During Twilight Sparkle and her friends' journey beyond Equestria, the Cutie Map has expanded to include the various locations they visited, including Klugetown, the pirate ship, and Mount Aris. Tempest Shadow, the former lieutenant of the Storm King, has left to travel Equestria and spread the word of the Storm King's defeat. Realizing that there are so many creatures beyond Equestria who know nothing about friendship, Twilight decides to open a friendship school. At the School for Gifted Unicorns, Twilight informs Princess Celestia of her plans, and Celestia gives her full approval and support. When Twilight bombards Celestia with questions on how to run the school properly, Celestia tells her that her time as Celestia's pupil has already more than prepared her. In addition, Celestia informs Twilight that her school plans must be approved by the Equestria Education Association —or E.E.A.— the leading authority on all school-related matters. When Twilight and Spike meet with the E.E.A.'s hard-nosed Chancellor Neighsay, Twilight assures him and his council that her friendship curriculum will make Equestria a safer place. Neighsay places an emphasis on teaching ponies rather than other creatures, but he and the council accept Twilight's plans and grant provisional approval for the opening of her school.
Some time later, the School of Friendship is officially opened near Twilight's castle. To realize her goal of teaching friendship to others, Twilight has appointed her friends as teachers and Starlight Glimmer as a guidance counselor. Some of the ponies are unsure about their qualifications to be teachers, but Twilight is confident that everything will be fine as long as they follow the E.E.A.'s guidelines. The school doors open, and Twilight's friends discover that she has invited not just ponies to be school students but also dragons, griffons, yaks, changelings, and hippogriffs. In her first address to the new students, Twilight welcomes them to the school and invites them to "Friends and Family Day" so that students' family members can see their education progress. However both teachers and students are bright-eyed and hopeful for the classes to come, and as time goes on and Twilight forces her friends' lessons to be in accordance with the E.E.A.'s guidelines, the fun that the rest of the Mane Six and the students are having rapidly dwindles. As some of the students get bored and frustrated with their classes and teachers, they start to argue amongst themselves. With the Mane Six stopping the students arguing around them instead of learning about friendship, the ponies wonder if they are cut out to be teachers.
The next day, in Twilight's office, the ponies complain to her about their lack of teaching progress. But Twilight assures them that, despite their rough start, they will be fine as long as they stick to the E.E.A.'s guidelines. Starlight suggests a teaching method not outlined by the E.E.A., but Twilight says Chancellor Neighsay will be visiting later for Friends and Family Day to make sure the guidelines are being followed. Later that day, Chancellor Neighsay arrives at the School of Friendship to check on Twilight's progress. Rainbow Dash informs Twilight and Starlight that six of the students are gone, but the three of them keep this a secret from Neighsay and distract him. At the lake outside the school, ponies and various other creatures gather together for Friends and Family Day. Just as Twilight and Neighsay join them, the students return from ditching class, with the Changeling student taking the form of a giant insect-like monster. The event attendees erupt into a panic, and Neighsay believes the school is under attack. When the students inadvertently make a mess of Friends and Family Day, Neighsay perceives it as an act of aggression, and Twilight apologizes on behalf of her students. Neighsay is shocked to learn that Twilight has non-ponies among her students, calling the other races "dangerous" and believing they would use Twilight's lessons against Equestria. Thorax, Ember, Prince Rutherford, Seaspray, a Hippogriff representive, and Grampa Gruff take extreme offense to Neighsay's insinuations and pull the students they represent out of the school. Because Twilight failed to meet the E.E.A.'s high-reaching standards, Chancellor Neighsay shuts down the School of Friendship and puts a magical lock on its doors.
Following the closure and discrediting of her School of Friendship, Twilight Sparkle falls into a depression and refuses to get out of bed. After upsetting her friends and making enemies out of Equestria's allies, she feels like a failure as the Princess of Friendship. Her friends enter to try and cheer her up, but Twilight says she needs time to be alone and think. Outside the closed-down school, Starlight Glimmer appears before Twilight, but instead of trying to cheer her up, she tells Twilight what she did wrong. Starlight tells Twilight she gave up too easily and should stand up for what she believes in, regardless of what anyone says. Twilight is unsure about going against Chancellor Neighsay and the E.E.A.'s rules, but Starlight says, as the Princess of Friendship, she should write her own rules. Taking Starlight's words to heart, Twilight meets with the rest of her friends in the castle throne room and declares she is reopening the school. After the lack of success in their lessons, the ponies are nervous about trying again, but Twilight allows them to teach their own way this time instead of the E.E.A's way. While Twilight deals with the school's discrediting, her friends go to get their students back.
At Yakyakistan, the Dragon Lands, the Changeling Kingdom, Mount Aris, and Griffonstone, the Mane Six attempt to make peace with the creature representatives that Neighsay offended in the previous episode and ask to enroll the six students, named Yona, Smolder, Ocellus, Silverstream, and Gallus, at the school again. Unfortunately, the same students went missing. With the students missing, the leaders of the different races of Equestria gather at Canterlot Castle. According to Seaspray, the students left notes saying they didn't want to say goodbye after the school was closed and ran away to stay together. Believing someone helped them accomplished this, the leaders all start accusing each other of hiding the students. Princess Celestia tells Twilight to find the students quickly before war breaks out between all the races. Back at Sugarcube Corner, the Mane Six, Starlight, and Spike try to figure out where the students have gone. Sandbar enters to buy a large quantity of cupcakes from Pinkie Pie. Upon realizing the ponies are looking for his friends, he immediately gets nervous. Applejack and Rarity recall Sandbar picking up a large amount of apples and pillows earlier that day and deduce they'll find the other students if they follow him.
Gallus, Smolder, Ocellus, Yona, and Silverstream hide from their students and leaders at the Castle of the Two Sisters. When Sandbar returns with the supplies he picked up in Ponyville, the six friends eat cupcakes together and have a pillow fight. However, their food draws the attention of a small porcupine creature called a pukwudgie. Ocellus transforms into a pukwudgie herself to try and befriend it, but the creature turns feral and calls other pukwudgies to its side. When Yona attacks them, they shoot their quills at the six friends, forcing them to take cover. Before the pukwudgies can attack again, the six friends are rescued by the Mane Six, who round up the little creatures and send them flying with Pinkie's party cannon. The six students are impressed by their teachers' skills, and the Mane Six are relieved to see their students unharmed. Now that they have been found, Ocellus fears their teachers are going to send them back home, but Twilight has another idea. Impressed that the students have already learned about friendship outside of their school lessons, Twilight asks them to return to the School of Friendship. The students agree under the assurance that their lessons won't be as boring as last time.
The Mane Six and their students return to the school in time for the arrival of Princess Celestia and the race leaders. The students decide to stay at the school, much to the surprise of their leaders, and Twilight uses her magic to break Chancellor Neighsay's seal on the doors. When Neighsay appears to investigate the broken seal, Twilight and her friends tell him to step aside so they can resume classes. Neighsay angrily refuses to allow the school to be reopened, insisting that its closing was for the greater good. Twilight declares that even though the School of Friendship is not E.E.A.-accredited, it is an independent institution with its own set of rules that do not need the E.E.A.'s approval. Neighsay insists that changing the rules for such a diverse group of students will not work, but Celestia says the same thing was once thought about Earth ponies, unicorns, and Pegasi. With the belief that Twilight's school could one day destroy Equestria, Neighsay leaves in a rage.
With the School of Friendship officially reopened, Twilight and her friends rejoice with a group shot of the Mane Six and their students. In the end, Ember, Rutherford, and the other leaders allow the students to remain at the school. Grampa Gruff refuses at first, but after enough of Gallus' begging, he relents. As Celestia and the other leaders leave, Twilight and her friends head inside the school to begin their lessons.
Role in the series
The School would become famous for defying the will of the EEA, to the point that Neighsay would lose his credibility as chancellor, leading to the group's disbanding in the name of reevaluation, and Neighsay is banished for treason to the Map. Thus the school will soon start inviting more interracial students along with interracial teachers.
- High Chancellor University- The former unicorn head of the EEA who disbanded it upon Neighsay's crimes and now supervises the School of Friendship.
- Yakhalla- The former Yakotaur of Legend cured of corruption. Assigned to Magic Class.
- Spiracle- An elderly changeling from the hybernation temple of King Seta that is assigned to Culture Class, and later gains a Changeling teaching assistant named Vertex.
- Entropy Whirlwind- A former ancient pony turned Draconequus. Assigned to Counter Magic Class.
- Koningin- An antelope from the Equestrian Grasslands assigned to being a gym coach and has a dik-dik assistant named Aloe, who is acrobatically gifted, but very clumsy.
- Professor Spoonful- An Abyssinian Spoonbill historian and archaeologist from Klugetown that is assigned to history class with his curators and assistants Pines and his pet Dragon Moths, mainly guarding the Amulet of Aurora, the Talisman of Mirage, the Helm of Yksler, the Crown of King Grover, Knuckerbocker's Shell, and Clover the Clever's Cloak, which he obtained for the school as tokens of their races' respective cultures.
- Professor Buzzord- An Abyssinian Vulture crackpot scientist and inventor from Klugetown that is assigned to science, and after countless mishaps of endangering students, will eventually get 6 assistants in the form of an Abyssinian bearded dragon named Beardy, an Abyssinian rooster named Volat, an Abyssinian bobcat named Lascivus, an Abyssinian goliath frog named Groc, an Abyssinian basalisk lizard named Lanx, and above all, Buzzord's number one fan (And by tecnecally, only fan currently) and equil Kludgetownian Inventor or basicly recycles Buzzord's attempts but improves apawn them with actual appresiation, with mixed views from the Professor himself because of both being flattered by this and admired her, but also abit touchy about her "Using my work without permission", A beautiful Abyssinian Great Blue Heron Bird, named Euri Kaki, nicknamed as "Miss Eureka", of which, to the Professor's current lack of proper understanding, Euri has great personal feelings for the professor after years of personal sympathy turned into desires for love in being able to reckindise the professor's potaintional held back by his eccentric and poor-hindsighted behavior.
- Electross- A defect Cragmite who joined to teach the larger United Universe culture. Though he ended up mostly feeling lonely and had desired an assistent like most of the other teachers, and eventually got that in Cynidress.
- Barktrot/Barkrot- Formerly named Barkrot, She's a Peryton magician for nature magic who is a assigned to teaching about how to remove dangerous ailments in a crazy magical world, magical or otherwise, along with being a teacher for humility. She's also serving as a school nurse due to her reknowned healing abilities, which is a godsend to the school due to the Antics of Professor Buzzord alone.
- Olhar- A Stone-Eye Cyclops and once guardian of the Founders of Equestria during enslavement to Bishop Dipper, but then freed and now serves as Campus Security for the School and would ward off intruders and enforce the ban on any that commited prior trouble to the school.
- Youyi Chop- A Kirin from Xiaomia and the school's teacher for inner peace.
- Mister Gallopus- The Centaur Teacher of math class.
- Master Doubler- The Bicorn Teacher for social studies.
- Mister Ostricherd- The Griffin Teacher for economics class.
- Miss Clamuso- The Seapony Teacher for water training.
- Mister Halferson- The Impure Hippogriff Teacher in charged for genectic science.
- Miss Doe- The Deer Teacher in charhe of plant class.
- Doc Alps- The Alphyn Teacher for travel studies.
- Lord Pyrope- The Dragon Teacher for law and order studies.
- Mister Strype- The Zebra Teacher for land studies.
- Mistress Calico- The Abyssinian Teacher for survival studies.
- Master Minos- A Minotaur and a stronger and less clumsy assistant coach for Koningin.
- Miss Bushy- The Bushwoolie Teacher for Tribeal interaction training.
- Mistress Honeydew- The Breezie Teacher for Breezie Interaction Class.
- Mister Yakski- The Yak Teacher for Weaponry class.
- Master Infinity Clover- The Pure Hippofeonix teacher for bravery class and martial arts.
- Yona- A cheerful yet clumsy yak and a smart one who is Prince Rutherford's niece.
- Gallus- A sarcastic parrot-like griffin who joined the school to solve griffin relations since the events of The Convocation of Creatures.
- Silverstream- A hyperactive hippogriff and Queen Novo's niece who enjoys seeing new things after her underwater isolation. She came to the school to heal hippogriff relations since Twilight tried to steal from them.
- Ocellus- A shy Changeling who has a bit of a good mind and tactical brilliance to her and has been easily confused in gender.
- Smolder- A gruff dragon who joined the school against her own will by Princess Ember to establish good dragon relations.
- Sandbar- An easygoing Earth pony from Horseshoe Bay who joins the school to help his crush's race.
- Shore Joy- A very social and bubbly seapony from Horseshoe Bay who fell in love with Sandbar and joined him and the school to help her race.
- Cozy Glow- A Pegasus filly and valedictorian of the school who is secretly seeking to take over the power of friendship magic by making friends with everyone.
- Daylight Glint- A reformed clone of Twilight.
- Applesauce- A reformed clone of Applejack.
- Giggle Glee Candy- A reformed clone of Pinkie.
- Antique Jewels- A reformed clone of Rarity.
- Fairweather Skip- A reformed clone of Fluttershy.
- Moonbow Jounce- A reformed clone of Rainbow Dash.
- Gaster- A changeling bully who mainly picks on Ocellus because he has a crush on her, and has a smarty attitude, being a lone ranger that doesn't trust royal figures or superiors who 'think they know what they're doing'. He was taken to join the school by Pharynx that, though otherwise being considered his faverite drone because how aggressive he is, it was because Thorax is worried that his attitude would leave him vulerable to League manipulation, so he was taken to the school to avoid it.
- Quartz- A young purplish dragon exactly near Spike's age who was brought to the school as a result of being oppressed for her love for friendship, especially since a puberty-like molt got her ousted from her home when her dragon traditionalist parents saw that as a perfect excuse to not put up with her "Preachy ways". One of Ember's Dragon Elites, Ballista, saw pity on her and took her to the friendship school under Ember's approval since the school already had a dragon representive in Smolder.
- Skyceria- A Peryton younger sibling of a beloved though rather snarky and self-obsorbed older sister, Princess Prominade, that always hogs the spotline and not treating those like the two service deer of her royal chariot all that well for albeit legit incompidence, along side the fact Prominade is like Mad Munchkin's Mary Sue cranked up to 11000! Skyceria is a lover of flight and is typically very well inversed with animals, albeit has yet to master all creatures' hapits and behaviors. Skyceria does care for her sister, but her sister's massive ego prevents and stagnates any serious bond the two would have, and she hoped that by going to the friendship school, Skyceria would find a way to succeed in understanding her own sister.
- Caster and Buster- Gaster's revived and cured brothers in due to Labrum who the duo initionally helped, until Gaster was able to win his brothers over and allowed them to be purifived. Caster is now a heavy purple color while Buster is Inigo. Caster is a smartass wise-cracker while Buster is abit of a doofus, but Gaster is the one who's the ultamate brains of the outfit. The duo are often basicly trouble-making class-clowns as even purifived, their old hapits of being trouble-makers are dying very hard. The duo are extreme lovers of pranks, which means they would get along well with La Broma.
- Little Dipper- A former pony now a purifived Taraxippus and the son of Bishop Dipper. Little Dipper came to have the mannorisums of DBZ Abridged Dende that often brings passive-agressive cynicisum to the eccentrisities of others and reads others like open books.
- Clyde Shockerwing- The young cousin of Sid the Yellow Wyvern Dragon, who often tends to really like to party, giving him the nickname, "Party Hardy". His love for parties would make him a popular student in the school, along with the fact that he is releated to Sid, who earned himself quite the hero reputation, along with being a reknown daredevil.
- Rhabdom- A mantis shrimp and emperor shrimp-like Sea Changeling formerly lost in the Tree of Harmony caves trying to find herself.
- Polarity- The magical reindeer daughter of King Boreal and a Hearth Reindeer in training who came to the School of Friendship to better understand the job.
- Phoebe- A griffin-phoenix hybrid with the powers of a phoenix and a fiery temper.
- Snipeskale- A teenage gargoyle from the Badlands who is too brave and tough for his own good.
- Splash Wave- An eccentric seapony who has a magic crystal knife and can break the fourth wall.
- Wavelength- A socially-poor male seapony and boyfriend of Splash who came from an Abyssinian sentient aquarium.
- Sepia- A krakonling and former early-preistess for the Krakons' former connection to the Mindflayers until the defeat of Kala Mari.
- Papyrus- A young Panan satyr orphan who lived on the streets with his magic pan flute 'Remedy' after his magician parents died.
- Mixie- A Star Butterfly-esque Draconequus and love rival of Topsy and Turvy, the two head royal guards for Discord's parents.
- Gamey Clouds- An annoying yet good-hearted hippalectryon.
- Magnolia- A diligent and serious doe from Thicket.
- Fable- A valley-girl centauress.
- Epoch Bowshock- A personally-inconsistent bicorn.
- Qi Opium- A tomboyish and adrenaline-drunk feonix.
- Peanut- A comically cute Bushwoolie.
- Glyph Fire- An intelligent but snarky Alphyn.
- Centauri- A centaur bully and Fable's crush.
- Lilac Limaçon- A mute Bicorn mare who is shy but strong.
- Gawk- A mean parrot-like griffin and old friend of Gallus.
- Wetwater- A highly social and curious merpony.
- Derecho Douse- A brooding dark winged wolf.
- Bract- A deer buck and Magnolia's love interest.
- Or- An adventurous and ambitious goldhorn.
- Acacia- A young clumsy but kind giraffe that joins the school with other new Potamian students after a field trip/evaluation in the Equestrian Grasslands.
- Zizi- A young cool but stuckup zebra that joins the school with other new Potamian students after a field trip/evaluation in the Equestrian Grasslands.
- Findi- A young hesitant and very stressed dik-dik that joins the school with other new Potamian students after a field trip/evaluation in the Equestrian Grasslands.
- Ebony- A young boastful and overconfident okapi that joins the school with other new Potamian students after a field trip/evaluation in the Equestrian Grasslands.
- Persimmon- A young wise and wayward antelope that joins the school with other new Potamian students after a field trip/evaluation in the Equestrian Grasslands.
- Hectare- A young annoying and obnoxious wildebeest that joins the school with other new Potamian students after a field trip/evaluation in the Equestrian Grasslands.
- Tepuy- A young aggressive rhino that joins the school with other new Potamian students after a field trip/evaluation in the Equestrian Grasslands.
- Mangrove- A young disgusting and gluttonous but bold and strong hippo that joins the school with other new Potamian students after a field trip/evaluation in the Equestrian Grasslands.
- Kopje- A young clumsy and speech-impeded elephant that joins the school with other new Potamian students after a field trip/evaluation in the Equestrian Grasslands.
- Waratah- A young mostly-mute and magic-curious Quinkan who needs enlightenment after her hard upbringing.
- Dips- A baby Ursa, or anthropomorphic Ursa Minor, exactly Spike's size, who hails from the land of Constellatia.