The situation was revealed to be a comic book Nermal was reading during a cookout with the gang. Nermal is really excited about getting the next 100th edition issue. Garfield's friends go to the Comic studio to work their new strip, except Garfield who wants to finish all the hot dogs. Nermal gets the new Pet Force issue from a news stand, with Garzooka jumping out of a comic book afterawards. Garzooka heads for Jon's house, and is told where Odie, Arlene, and Nermal are by Garfield. Garzooka gives Garfield the Klopman Crystal as well, telling him to protect it. Curiously, the pages of the comic book show exactly what is going on in Comic Strip World with Garfield & his group, but pages of future incidents are blank until the incidents occur.
In the break room at the Comic Studio, Nermal, Arlene, and Odie notice Garzooka behind them. Garzooka hands them the serums, asking them to help him stop Vetvix, but they don't change immediately after they drink the serums. However it's time for Odie, Arlene, and Nermal to go to work and Garzooka follows. Meanwhile, the real Garfield is enjoying a relaxing day all to himself, but is captured by Vetvix (who appeared in Comic Strip World earlier), who tourtures him for the Klopman Crystal, but to no avail (because Garfield is a cartoon character). Garfield tries to protect the Klopman Crystal, but it is taken by Vetvix and orders her guards to get rid of Garfield.
Back at Comic Studio, the gang is interrupted by Vetvix, who crashes her war ship into the Comic Studio, and zombifies most of the characters at the studio. Nermal, Odie, Arlene, Jon, and Garzooka escape to the back alley. Garzooka is wondering why the serums haven't taken effect yet. He notices Garfield falling from sky, when Odie, Nermal, and Arlene turn into their Pet Force counterparts, the effects of the serums having been delayed. They plan to bring down Vetvix's ship using the antenna on top of a tall tower nearby. Vetvix's ship reverses, causing a bill board to break to pieces. The Pet Force hide under one of the broken pieces of the bill board and escape while being chased by zombies and manage to reach the tower by crashing through walls. Eli saves Garfield from Vetvix, by making the air vent suck him in while Jon and a trash can were scrambled then becoming zombies. Vetvix causes chaos, zombifying all of Cartoon World. Eli and Garfield manage to find three survivors: Wally, Wally's wife Bonita, and Betty. Garfield decides to name himself and the survivors "The Crazy Crew" and form their own plan. Meanwhile at the tower, Garzooka realizes the zombies are too much for the Pet Force. Luckily Garfield and Wally disguise themselves as Garzooka, and get the zombie's attention. The real Garzooka and the Pet Force go to the antenna and use it to bring down Vetvix's ship. Meanwhile, the zombies chase Garfield and Wally to the Comic Studio, and Eil opens the pit in the filming area, in which the zombies fall into. Meanwhile, at the tower, Vetvix shoots the Moscram Ray Gun, using the super scramble mode, at the Pet Force.
Emperor Jon and Professor Wally break free (by the Professor's monocle that Garfield put on the windowsill earlier), and take over the ship, flying into the air, making Vetvix fall off. However, she makes a giant monster by shooting the ray gun at most of the buildings in Cartoon World, and decides to use the monster to destroy everything and get back her ship. Meanwhile, Vetvix's ship lands near the back alley of Comic Studio, and the Crazy Crew meet them, who let Garfield enter the ship. The ship flies above the monster, and Garfield jumps off. By using the power of the Super Scrambled Pet Force, and the dropped Moscram Ray Gan, Garfield defeats the monster, along with unscrambling the Pet Force. Garfield and the "Crazy Crew" surround Vetvix, and she backs up into a corner called the "Smile Section", which Betty invented. Garfield shoots Vetvix with the Moscram Ray Gun, and Vetvix becomes a nice woman, the perfect spouse for Emperor Jon. Eli opens the pit and Garfield unscrambles the zombies. Garzooka gives Arlene, Odie, and Nermal the red serums, and drink it. Emperor Jon and Queen Vetvix start their honeymoon after Emperor Jon immediately forgave her. Garfield finally wins Arlene's feelings, and two gaze at the stars. Suddenly, a trail of stars goes under them and they float into space and dance, before returning to Earth, and the film ends.
In the post-credit scenes, While watching Emperor Jon's wedding, the gang watch a video (showing that the real Pet Force is back) at the Comic Studio. They notice that Betty is there too, and realize that she followed Garzooka to Dorkon. It looks like there will have to be a new assistant to Charles, the director of Comic Studios, which Nermal is eager to take.
Frank Welker as Garfield/Garzooka
Gregg Berger as Odie/Odious
Audrey Wasilewski as Arlene/Starlena
Jason Marsden as Nermal/Abnermal
Vanessa Marshall as Vetvix
Wally Wingert as Emperor Jon/Jon Arbuckle
Neil Ross as Professor Wally/Wally Stegmen