The book begins by telling the reader about how Stuart was born to a family in New York City. Stuart's family members gradually adapt to the social and cultural changes that having such a small child brings about, along with have to change some of the physical aspects of their home to facilitate Stuart's living there.
Later, Stuart is exercising and he accidentally gets himself stuck in one of the house's window-blinds. Taking advantage of Stuart's state of entrapment, the family's malevolent cat, named Snowball, steals from Stuart his hat and cane and places them right outside of a rathole; this panics both Stuart and his family. Stuart's brother George eventually, accidentally sets Stuart free.
After this bout, Stuart partakes in a sailboat race that takes place in Central Park. Immediately after this, Stuart befriends a bird that is named Margalo, and Margalo is subsequently adopted by the Little family. After taking her in, Stuart bravely and constantly protects Margalo from Snowball, who frequently tries to eat her, but, thanks to Stuart, never succeeds. Margalo repays Stuart for this when she helps Stuart escape from a garbage can inside of which he is trapped and which is being shipped off to sea to be desposed of in the ocean.
At some point after rescuing Stuart, Margalo is warned that one of Snowball's friends is going to eat her. Because of this, she flees the Little house. Missing her immensely, Stuart sets out to find her. A dentist, also being a friend to the family, lends Stuart a gasoline powered model car. Said dentist was also the owner of the sailboat that Stuart raced in the sailboat race in Central Park. After acquiring the car, Stuart leaves his hometown to see the world and to find Margalo.
During his travels, Stuart works for a short time as a substitute teacher before he comes to a town by the name of Ames Crossing. While he is in this town, he meets a girl named Harriet Ames, who is the same height as Stuart is. They are interested in each other, but their relationship does not work out.
As the book concludes, Stuart has not yet found Margalo, but is exceedingly sure that he will.