One seemingly normal day, SpongeBob and Squidward are on their way to work when huge asteroids start raining down on Bikini Bottom. A huge drop of goo falls on Squidward, causing the top part of his face to turn orange and become a cyclops of some sort. He becomes a zombie, chasing SpongeBob around the perimeter of someone's house until Patrick intervenes. Jimmy Neutron then arrives to take them to the Mawgu lair. Soon, the gooey creatures spawning from the asteroids start taking over Bikini Bottom...
SpongeBob and Patrick explore the vast Mawgu lair, where they meet Danny Phantom and Tak again and the new Evil Syndicate composed ofTechnus, Beautiful Gorgeous, Traloc, and Plankton. Zim and Dib then arrive, with Zim joining the good guys, and Dib joining the Syndicate. They make a plan to stop the gooey creatures, identified as Morphoids, when the Wise Old Crab arrives to inform them about the technology in the lair. Jimmy is able to figure it out, and fits everyone with weapons fitting their personality: Jimmy receives some sort of helmet and a tennis racket, SpongeBob gets a bubble blower, Danny receives a device that allowed him to partly clone himself, Tak is given a staff, and Zim receives a plunger (or as he refers to it, "It is a Plunger of DOOM!!!"). Meanwhile on the evil side, Technus receives an arm blaster, Plankton is given a hammer that allowed him to grow (about to the height of Jimmy, Zim, and SpongeBob), Traloc receives a pouch of magic potions, Dib is given a gun-like balloon launcher, and Beautiful Gorgeous receives a heart-shaped megaphone.
They go through Bikini Bottom, and they meet Bubble Bass down with the last Krabby Patty he had in his bag. Checking if he has some more Krabby Patties in his bag, a blob of goo lands on his last Krabby Patty he had in his hands. He shoves the Patty with goo into his mouth, which makes him grow gigantic and become a zombie. They travel throughout Bikini Bottom, where the group battles an army of Morphoids, free Gary, Squidward, and Patrick from the Goo. They defeat this new menace by feeding him Krabby Patties (which ironically turned him into a zombie in the first place). When Bubble Bass can't eat anymore Krabby Patties, he vomits a large amount of goo... which land on SpongeBob. SpongeBob is then doused in goo, but doesn't mutate like the other people on Bikini Bottom. At the lair, when he was done being washed off the goo, he suddenly then says in an evil voice: "Your world will end! My Globs of Doom will rain over your world... and take control... Bwaa!! Haa!", while the Wise Old Crab informs them that a huge robot called the Vessel of Portentia is hidden in the Mawgu Lair, and requires four special components to power it up.
The next world they go to is Zim's town, where Gir was playing with a taco which happened to be the first component of the Vessel Of Portentia. When Zim demanded Gir to drop the component, a blob of goo rained down, landing on Gir, mutating him. Gir picks up the component, and runs away. While They manage to free Ms. Bitters, Gaz, and Professor Membrane, then face the corrupted Gir, who has sprouted several mechanical tentacles and has the ability to summon Morphoids from his very being, using his house to fight. He soon tires out of attacking the heroes, and is then beat up out of being possessed. The house drops some goo, which lands on SpongeBob (SpongeBob remarks "Hey! Is there a sign on me that says 'Goo Sponge'?"). When they retrieve the first piece, SpongeBob says: "We've got it! The first piece of the Vessel of..." which is then interrupted by the same evil voice that happened earlier. Saying: "... but it won't be enough to stop me from..." SpongeBob then talks in an even deeper voice, saying: " ... SMUGGLERING your insignificant planet!" The group finds out that the absorption of goo in SpongeBob's body is creating a wavelength so the leader of the Morphoids can talk through him. SpongeBob snaps out of it when he smells a Krabby Patty Patrick was holding.
They venture to Amity Park, where Morphoid asteroids rain on the citizens, freeing the Ghost Dog in the process. Not soon after, a blob of goo falls on its head, resulting in him too being mutated. He goes on a rampage through town. After freeing Dash, Tucker, and Jazz, they fight the Ghost Dog at a power plant, where Ghost Dog crashes into the wall, which his goo flies off. Right as the goo was about to land on SpongeBob, SpongeBob says: "I'm no Shaman, but I now what's gonna happen next.". SpongeBob is yet again splattered in goo. They gain another piece of the Vessel, and it is at the lair that Globulous Maximus, who has just revealed himself, once again talks through SpongeBob, saying: " Little yellow one... you are soft and squishy... and tiny absorbent. I... am Globulous Maximus! Ruler of the Morphoids!... I speak... through you..." The ordinary Krabby Patty smell didn't make SpongeBob snap out of it, so Technus had to flick SpongeBob's nose so he could snap out of the trance. SpongeBob tells his group that he saw Globulous Maximus (a similarity to the word "Gluteus Maximus") which was the ruler of the Morphoids, SpongeBob says he will bring Doom, Gloom, and Evil.
They then head to Retroville, where the goo has turned Jimmy's girl-eating plant into a monstrous giant, and prepares to eat Cindy whole (expectedly). After defeating several more Morphoids and freeing Carl, Cindy, and Sheen, they fight the girl-eating plant at the mall. After being consumed several times (and beating up the plant's fragile heart), the team manages to defeat the girl-eating plant which spits out a giant glob of goo. SpongeBob easily avoids the glob, but another glob lands right on top of him. The third piece of the Vessel is retrieved, though. SpongeBob states that Globulous Maximus was only a few lightyears away from Earth and was preparing to send more gigantic Morphoids to destroy it.
Finally, they go to Pupununu Village and find the fourth componet of the Vessel of Portentia covered in goo. SpongeBob pokes the goo to try and free the component, but ends up being covered in goo. He grabs the componet and races to the Mawgu Lair.
Back at the Mawgu lair, the evil voice of Globulous Maximus says: "Square, yellow creature of happieness...you are unlike anyone I have met before... I... have grown tired of my gooey life... and for the first moment since the beginning of time...I... Globulous Maximus... choose to become something else... SOMEONE else, actually... I choose to become... you..." Globulous' speech is briefly interrupted when the regular SpongeBob asks: "Me?". Globulous then continues: "Yes, you... I like you.. you are good... you are happy... you are wholesome... like homemade bread."
The team quickly inserts the pieces of the Vessel of Portentia, and then speed towards space, where they confront and defeat Globulous Maximus, who is a large asteroid himself with floating arms and a primary eye (along with several non-functioning others). After Globulous is defeated, the Evil Syndicate betrays the rest of the group because they wanted to capture Globulous for their own evil plans, taking over the Vessel of Portentia and ejecting the heroes from the robot. Globulous Maximus then opens up to the heroes, where he reveals that he was created at the beginning of the universe, the Big Sneeze (a similarity to the Big Bang), thus making him a huge orange booger. SpongeBob then asks why he was destroying worlds, with Globulous replying that he was distasteful of his form and thus took out his anger on others. SpongeBob then tells him to embrace who (or what) he is, and they throw Krabby Patties in his mouth to make him feel better. The group then wonders how they will stop the Evil Syndicate from taking over the Earth. Globulous states that he has an idea, and morphs into a huge, orange, and cycloptic version of SpongeBob.
Using this form, Globulous and the heroes manage to defeat the Vessel of Portentia on the moon, and it explodes in space, leaving the villains floating around. Dib thinks that this is the part where the villains retreat with their tails between their legs, but Plankton contradicts this statement, saying that it's the part where "the villains pound their fist and say 'Curses! Foiled again!'". Technus invites Plankton over to his hand, where he executes Plankton's statement, albeit with Technus pounding Plankton to a pulp on his palm.
Globulous returns the heroes to Earth, and says that he will right the wrongs in the universe, taking the moniker "SpongeGlob". The heroes bid him farewell, and SpongeGlob blasts off into space. Meanwhile, SpongeBob sneezes, and the goo finally exits from his body through his many holes. Patrick compares this moment to the beginning of the universe where SpongeGlob was born, while the Wise Old Crab then summons a typical "The End" sign.