The story is about the skid row denizens of Monterey, California, during World War II. As declining fish stocks are shutting down a previously rich fishery and the dependent canning industry, bums and prostitutes lead colorful and adventurous lives in a balmy seaside setting.
Doc, a self-employed marine biologist, lives in a dockside warehouse and researches octopi. Suzy DeSoto, a girl from the local bordello, is working there only out of necessity.
A collection of linked vignettes describes life on Cannery Row. It is depicted as an impoverished area inhabited by a motley band of people who have experienced failures, but somehow have found their niche and a community of strangely kindred souls.
Doc and Suzy don’t quite fit in, but are accepted. Mac and the boys gather frogs and sell them to give a surprise party for Doc, which turns into a brawl and breaks the tank housing Doc’s octopus collection. To make amends, they buy Doc a present of a microscope but mistakenly get him a telescope, instead.
A deeper mystery revolves around why Doc stays in Cannery Row. Suzy discovers that Doc was once a professional baseball pitcher but quit.
Another character, the Seer, spends his days playing his horn. He depends on the gifts that mysteriously appear, such as groceries. Suzy eventually learns that the Seer is a former baseball player whom Doc injured with a pitch to the head, and now Doc takes care of him. Doc and Suzy ultimately find love.