Everything was just fine in Comic Strip Land. Until Vetvix takes an invention called the molecular scrambler. Vetvix plans on turing the citizens of Comic Strip Land into molecularly scrambled slaves. Now Garzooka comes to Earth to make Nermal, Arlene, and Odie the new Pet Force to save the comic universe from Vetvix. But when even Pet Force can't stop this fiend, Garfield realizes he has to save the day.

Garfield (voiced by Bill Murray) goes to London with Odie to surprise his master, Jon Arbuckle (played by Breckin Meyer), who is in London to propose to his girlfriend, Dr. Liz Wilson (played by Jennifer Love Hewitt). Garfield inadvertently switches places with Prince, a royal cat who has just inherited a castle. They both look exactly alike (the same breed).

In the grand estate Garfield now calls home, he receives the royal treatment, including a butler and an international array of four-legged servants and followers. Lord Dargis (the main villain played by Billy Connolly), who is next in line to inherit the estate, wants Prince/Garfield (voiced by Tim Curry) out of the picture.

He makes many attempts to get rid of Prince/Garfield, one involving a vicious but dim Rottweiler. Eventually Jon, with the help of Odie, prevents Lord Dargis from trying to kill Prince/Garfield. Jon finds a newspaper and goes to Garfield, while Garfield and Prince meet each other for the first time. When Lord Dargis finds out that Prince is still alive he tries to kill him before anyone sees. Then he threatens everyone if they don't sign the papers to him. Odie and Jon end up saving the day, and Liz and Jon get engaged.

The exterior castle scenes were shot at Castle Howard in Yorkshire, England and some of the interior scenes like the main staircase were at the Greystone Mansion in Beverly Hills, California, and most film scenes were shot at London.