Phil, his wife Dottie, and their two children, Barbara and Billy, find themselves living in the lovely state of Maryland along with their pet Great Dane, Marmaduke. The story kicks off at a festive birthday celebration for Billy, where Marmaduke takes an unexpected leap from the second floor of their home straight into the backyard pool, creating a spectacular splash. Barbara captures this breathtaking moment on her phone, and to their surprise, the video quickly goes viral online.
This newfound fame garners the attention of a highly acclaimed dog trainer, Guy, who proposes to transform Marmaduke into a world-class show dog. Initially, the family is hesitant about allowing Marmaduke to compete. However, when Phil learns that the competition offers a stunning grand prize of one million dollars, he is convinced to proceed with the arrangement. As Marmaduke begins his training, he faces some initial hurdles, yet gradually starts to show progress.
In an effort to gauge Marmaduke’s skills, Guy enters him into a local dog show. During the setup preparations, Marmaduke meets an Afghan Hound named Zeus, who lures him into eating before the competition, resulting in an unfortunate bloating situation. Despite his discomfort, Marmaduke struts onto the field with determination, but disaster strikes when he releases an overwhelming cloud of flatulence, engulfing the spectators in a foul odor. In a desperate attempt to relieve his distress, he leaps into the air, landing in the winner's trophy and making a mess, much to the shock and dismay of those present.
Embarrassed and rejected, Guy refuses to continue training Marmaduke, leaving him feeling defeated and forlorn. In a moment of escape, Marmaduke runs away from home only to spot his family cat, Carlos, in a precarious situation in the middle of the road. Despite experiencing difficulty in bonding with his feline counterpart, Marmaduke rises to the occasion and decides to embark on an adventurous journey around the world, showcasing his heroic antics along the way.
This escapade eventually impresses Guy, who decides to take Marmaduke back under his wing for the upcoming World Dog Championship. During the competition, Marmaduke encounters Zeus once more, along with other formidable canines, including Mexican Welsh Corgi Juan Pedro, the glamorous pink poodle Shantrelle, and the muscular Staffordshire Bull Terrier Vinnie. The competition is structured into three challenging tasks. After successfully completing the second task, Marmaduke finds himself in an unfortunate scenario where he inadvertently lands on Guy, who is promptly hospitalized.
With their trainer incapacitated, Marmaduke's family rises to the occasion, taking on the role of his coaches. In the third and final challenge, the dogs need to deliver a unique performance, and Marmaduke joins forces with Billy for a delightful cowboy act featuring Carlos, which captivates the crowd. When it comes time to announce the winners, Zeus initially takes the honor. However, Marmaduke uncovers corruption, realizing that Zeus’s owner manipulated the scoring, leading to Zeus’s disqualification. This twist allows the zen-like Japanese Chin, Zhi, to claim the top prize.
As tensions rise, Zeus attempts to reclaim his trophy, but Marmaduke intervenes just in time. In the chaos, Marmaduke accidentally knocks over a platform where a cameraman is situated. In a brave act, he pushes his family out of harm's way, ultimately getting hit by the toppling structure. Initially believed to be lifeless, Marmaduke miraculously survives, triumphing at the World Dog Championship, and returning to a joyful reunion with his family, who then enjoy a happy life together.
In a humorous mid-credits scene, Zeus is apprehended by security and sent to a dog pound, where he faces the consequence of having his fur shaved and regrowing. Meanwhile, his owners Henri and Philipe receive their own reckoning as they are taken to jail.
