A Tree Grows in Brooklyn is set in Brooklyn's immigrant neighborhoods.

The novel opens in the summer of 1912 with eleven-year-old Francie Nolan sitting on the fire escape and looking at a Tree of Heaven in her backyard; it then moves back in time twelve years to the courtship of Francie's parents. The novel proceeds chronologically from this point onward, tracing the lives of Francie; her brother, Neeley; and their parents, friends, and relatives. The sights, smells, and sounds of Brooklyn street life permeate the novel, influencing Francie's moods and helping form her character during the nearly seventeen years covered in the story.