Marmaduke is a Great Dane living in rural Kansas with a cat named Carlos. His owner, Phil (Lee Pace), works for Bark Organic dog food. Phil is very strict, from Marmaduke’s perspective.

One day, Carlos tells Marmaduke that he overheard Phil saying that they were being transferred to Orange County. They move from Kansas into their new house in California. Phil’s boss, Don Twombly (William H. Macy), has the goal of getting Bark Organic into every Petco store in the country. Phil and Don meet at the dog park to discuss Phil’s assignment – an ad campaign to win over Petco. There, Marmaduke meets a beautiful Rough Collie named Jezebel (Fergie), whose boyfriend is Bosco (Kiefer Sutherland), a controlling and violent Beauceron with two Miniature Pinscher minions named Thunder and Lightning (Damon Wayans, Jr. and Marlon Wayans)…