Marmaduke (Owen Wilson) is a Great Dane with a passion for life, though his passion sometimes exhibits itself in the trouble Marmaduke manages to get himself in. When his owner Phil (Lee Pace) gets a job at a new organic pet food company, he uproots his family, including Marmaduke, from their family home in Kansas to a new life out in California. Phil's wife, Debbie (Judy Greer), and their family, are not happy with their new locale, and try to voice their concerns to Phil. Phil, however, is too busy trying to fit in at his new company and make a good impression to realize the frustrations of his family. Marmaduke, meanwhile, is also trying to fit in with his new peers, including a possible love interest. Can the family come together and find some way to be happy in California?