Garfield (voice of BILL MURRAY) is a fat, lazy and sardonic cat who thinks he's master of his domain, especially considering that his animal companion is the dimwitted dog Odie. Then there's the fact that his human owner, Jon Arbuckle (BRECKIN MEYER) is completely fixated on trying to figure out how and when to ask veterinarian Liz Wilson (JENNIFER LOVE HEWITT) to marry him.
Just when he's about to pop the question, Liz gets an invite to speak at an animal conference outside London. Realizing he can't miss his opportunity, Jon hops the next plane across the pond, unaware that Garfield and Odie have stowed away in his luggage.
Not far away, Prince the cat (voice of TIM CURRY) truly is king of his castle as he's just inherited his late owner's entire estate, much to the dismay of the woman's greedy nephew, Dargis (BILLY CONNOLLY), who wants to turn the place into a resort. Accordingly, and keeping his actions secret from Prince's faithful human servant Smithee (IAN ABERCROMBIE), Dargis bags Prince, drops him in the nearby river and goes about with his plans.
As Prince's animal subjects, including bulldog Winston (voice of BOB HOSKINS), try to find their leader, Smithee happens to spot Garfield in London, mistakes him for Prince, and returns him to the castle. Garfield initially thinks the worst, but when he realizes the royal treatment he's receiving -- including all the food he could want -- he changes his mind and quickly adopts to the posh lifestyle.
Similarly mistaking Garfield for Prince, Dargis then sets out to do what he can to get rid of the cat, including siccing attack dog Rommel (voice of VINNIE JONES) on him. At the same time, Jon has found Prince and mistaken him for Garfield, all while still trying to find the nerve and right time to ask Liz to marry him. From that point on, the two cats must deal with their new surroundings, eventually realizing they need to get back to their respective homes.