Kaz boldly asks the most popular girl in school to the upcoming school carnival but is rejected, and tries to save face by claiming he already has a girlfriend. Much to Oliver's chagrin, Kaz invites Skylar to accompany him to the carnival, her first venture into the "normo" world, in hopes of convincing everyone that she is his girlfriend. Meanwhile, Alan tries to prove his worth to his uncle Horace by attempting to cure Titanio, a superhero with amnesia.
Oliver uses his burgeoning medical skills at school when he performs CPR on a popular girl's poodle, which quickly elevates his social status much to Kaz's chagrin. When the popularity goes to his head, Kaz cuts Oliver down to size, literally, with a shrinking ray. Meanwhile, Horace cannot perform surgery on Citadel, an ailing superhero with an impenetrable metal exoskeleton, so shrunken Oliver is sent inside the hero's body to diagnose the problem.
When Kaz and Oliver meet Timeline, a superhero who has the ability to see into the future, they discover that villain Crimson Demon and his three brothers have a plan to destroy the world. Oddly enough, because Kaz whizzed through his pop quiz, these three events lead to a portal's opening for the freedom of Crimson Demon's brothers. The three events are: the fool will become the wise man (Kaz whizzing the pop quiz), knight will fall during the day (Oliver falling inside a knight costume), and the chord of dischord will be played (Gus). [1]
Kaz and Oliver are exhausted and stuck working the overnight shift during a lunar eclipse, when it is rumored that the freakiest patients come to the hospital. When Neocortex checks in with an illness that unintentionally traps people in their worst nightmares, Kaz and Oliver desperately try to stay awake and figure out how to save everyone from their nightmares.
Kaz's fantasy football team always loses, so he get's upset since he never wins at anything. But when Tecton rescues Oliver from another superhero's snot rocket, Kaz makes up a fantasy superhero league. At first, it's a success, but when everybody goes to stop a runaway Ferris wheel for points, a villain named Sonic Shriek gets the chance to destroy the Benjamin Franklin bridge, and two superheroes, Tecton and Captain Atomic, turn on each other. Thankfully, Sonic Shriek's plan is foiled by Tecton, Captain Atomic, Skylar, and Kaz. Meanwhile, Oliver teaches Horace about Normo football. When Alan says he knows more about football than Oliver, they settle their differences with a trivia contest. However, Oliver is distracted by Alan's partner, Adrian Peterson. In the end, Oliver and Horace lose, so they have to sing a song about Alan.
Kaz and Oliver must study for a Mighty Med exam that will allow them to learn deeper secrets of Mighty Med, but if they fail, they will be cubed. Meanwhile, Wallace uses an optical image replicator to turn Clyde into an identical look-alike of Kaz. Clyde successfully follows Oliver into Mighty Med, but when he tries to steal the missing half of the Dyad of Nebulon, Horace senses something is amiss, and sends the guards after him, just as the real Kaz walks back into Mighty Med. Horace catches a Kaz and thanks to Oliver, doesn't cube him, but erases his memory. The guards send out the Kaz, and the other Kaz appears. Oliver realizes that this Kaz is the real Kaz, and the other one was really Clyde (though he doesn't know its Clyde). Horace explains that the other half of the dyad is with a villain named Catastrophe, who upon being defeated split into two humans (Wallace and Clyde). Back at The Domain, Wallace is trying to recall Clyde's memory of Mighty Med, which was successfully wiped. Kaz and Oliver pass their exam, and learn the secrets of Mighty Med. Meanwhile, when Alan comes to Skylar for advice on a girl he likes, she suspects it's her, and tries to dissuade him, only to learn it was a nurse who's also an octopus.
When a freak accident suddenly gives edgy rock star Jade super powers at a concert, attendees Kaz and Oliver recognize a new hero in her, and introduce her to Mighty Med. Jade becomes the hero Remix with Kaz and Oliver's help, but Skylar isn't convinced she's a hero when she's very demanding of service. Skylar decides to teach her a lesson by having Titanio dress like Soul Slayer, a teleporting villain, to attack her during rehearsal. When the real Soul Slayer arrives, Jade must become a real hero to save a powerless Skylar from Soul Slayer. Meanwhile, Jordan and Gus learn they will be dissecting frogs in class and Jordan plots to steal it to save it from dissection, but when they attempt to retrieve Gus' ransom note, their teacher catches them and reveals that when she discovered it was gone, she assumed they were trying to save it and told a local animal rights organization who will give the savior one thousand dollars, which goes to Gus since Jordan made him take the blame, much to her disappointment.
It has been nearly 1 year since Skylar, Kaz and Oliver became friends and Kaz and Oliver throw a party to celebrate their friendship. However, the boys learn not only is Skylar is in danger of losing her powers forever but she will also die. The boys help Skylar when in order for Skylar to reclaim her powers, she has to fight her nemesis The Annihilator.
After witnessing Skyler turning evil and loyal to the Annihilator, Kaz and Oliver run for it, only to be captured and locked up by her.
Oliver grapples with an internal conflict as he walks his mother down the aisle. Meanwhile, Kaz and Skylar struggle to protect the Arcturion from all the villains it beckons.