As the celebration to mark Villain Ville being closed off from Super Hero City turns into a disaster area, Iron Man, Falcon and Wolverine do battle with the Mole Man to retrieve an Infinity Fractal. Meanwhile, Ms. Marvel leads Hulk, Thor, Silver Surfer, and Storm in battle against Mole Man's creatures, Manoo, Megataur and Tricephalous.
When the city is attacked, the squad investigates, only to find that a little girl named Brinny Bratten, who had a fractal stuck in her tiara, that gives her a large and terrifying power over reality. The Heroes For Hire are helping the Squad find her father, while Doom plans to use the chaos to his advantage.
When he is tired of all he can take with the Super Hero Squad, Wolverine joins up with the internation All-Captains Squad (consisting of Captain America, Captain Australia, Captain Brazil, Captain Britain, and Captain Lichtenstein) as Captain Canada where he helps them fight Plantman in the Amazon. Meanwhile, the rest of the Super Hero Squad have an embarrassing encounter at Ringmaster's circus when Doctor Doom sent Abomination and MODOK to recruit Ringmaster.
When M.O.D.O.K. gains the power of an Infinity Fractal, he robs Dr. Doom of his powers and takes over as leader. Loki learns of this and decides to ally himself with M.O.D.O.K., forcing Dr. Doom to join forces with the Super Hero Squad in order to defeat M.O.D.O.K. and reclaim his rightful place as leader.
Dr. Doom is fed up with the Super Hero Squad constantly foiling his plans, so Enchantress decides to help by casting a love spell on Thor to make him fall in love with her. However, the love spell accidentally hits Ms. Marvel instead, causing her to fall in love with M.O.D.O.K. Meanwhile, Skurge intends to defeat Thor himself so Enchantress will love him.
When Baron Mordo possesses Iron Man turning him into the Iron Menace and escapes from the Dark Dimension, he plans to take over Super Hero City and Villainville. When Wolverine, Falcon, and Redwing end up under Baron Mordo/Iron Man's control, Hulk, Silver Surfer, and Thor must team up with Doctor Strange and Valkyrie to form a team of Defenders and stop Baron Mordo's evil plot. Doctor Doom and MODOK reluctantly help them when Iron Menace takes control of Abomination.
When a smilodon is brought to Super Hero City from the Savage Land, a mysterious jungle lord named Ka-Zar shows up stating that the smilodon is actually his companion Zabu. When the Super Hero Squad encounter Ka-Zar, they learn of his mission and help him rescue Zabu. Meanwhile, Doctor Doom sees the Star Quartz (which will bind and merge any metal in the presence of Vibranium) around Zabu's neck and sends Toad, Thunderball, Sabretooth, and Batroc the Leaper to steal Zabu in a plot to reforge the Infinity Sword.
The Mayor’s re-election bid goes awry when Egghead wins by a landslide (thanks to a little mass mind-control). But his reign at city hall makes life in Super Hero City a bureaucratic nightmare for heroes and villains alike. Wolverine and the Mayor are up against every hero and villain in a desperate attempt to free everyone from Egghead’s control and stop the villains’ planned invasion.
Doctor Doom sends his "Team Toxic" (consisting of Pyro, Trapster, and Zzzaz) out in a Fractal-retrieving activity at the north pole only to run afoul of Iron Man, Thor, and Wolverine. While Flatman and Reptil lecture about the polar ice caps, the world starts flooding after Trapster sets off their super-spinner machine to self-destruct. Now Iron Man must convince Iceman to help save the day.
It's Captain America's birthday and all he wants to do is celebrate it with his fellow Super Hero Squad members and Nick Fury. In order to show his minions what real villainy is like, Doctor Doom thaws out the WWII villain Red Skull. Captain America isn't pleased to find his old enemy up to his old tricks while Doctor Doom isn't thrilled about Red Skull's enormous ego.
With Galactus attempting to eat the Skrull Homeworld and the Silver Surfer nowhere to be found. The Super Hero Squad must hold off the devourer while finding their ally (who is slowly being corrupted by the Infinity Sword) who turns out to have delayed Ronan the Accuser from coming to the Skrull Homeworld's aid.
Enchantress places a love spell on Odin in an attempt to become queen of Asgard, but a forgotten rule forces him from the throne and makes his son Thor king instead, which both she and Loki try to take advantage of. Meanwhile, Magneto and Quicksilver discover Wanda joining with the Super Hero Squad and hitch a ride to try and take her back from them.
After being thrown into a portal by Dark Surfer, Falcon and H.E.R.B.I.E. find themselves in an alternate reality where Scarlet Witch is an evil emperor who rules the world. With help from an elderly Magneto and a strong Reptil, Falcon and H.E.R.B.I.E. try to convince Scarlet Witch that she is good and let the world be in peace.
After being thrown into a portal by Dark Surfer, a powerless Iron Man finds himself stranded on a world of monsters. There he meets Man-Thing and Werewolf by Night and battle Dracula and a gang of mummies led by N'Kantu, the Living Mummy. Later, it is revealed that Werewolf’s girlfriend Ellen was turned into a vampire prior to their arrival. As Iron Man tries to figure out how to leave to battle Dark Surfer, the trio of monsters declare they will form the “Supernatural Hero Squad” to save innocents on their world.