The dog is poorly behaved and destructive, and the book covers the issues this causes in the family as they learn to accept him in addition to their grief following Marley's death.

Told in first-person narrative, the book portrays Grogan and his family's life during the 13 years that they lived with their dog Marley, and the relationships and lessons from this period.

Marley routinely fails to "get the idea" of what humans expect of him; at one point, mental illness is suggested as a plausible explanation for his behavior.

The strong contrast between the problems and tensions caused by his neuroses and behavior, and the undying devotion, love and trust shown towards the human family as they themselves have children and grow up to accept him for what he is, and their grief when he finally dies from gastric dilatation volvulus (a stomach torsion condition) in old age, form the backdrop for the biographical material of the story.

In the autobiography, Grogan states that the eulogy he wrote in his newspaper following the death of his dog received more responses than any other column he had written in his professional life up until that point.