When the novel opens, Francie is eleven years old. It is 1912, and the Nolan family lives in an apartment in the Williamsburg section of Brooklyn. In the courtyard is a tree, called the Tree of Heaven, which always grows, regardless of whether or not it is watered. It even grows in cement, but only in the poorest neighborhoods.
Book I relates the events of one Saturday in Francie's life, as she and her brother collect scrap junk to sell for pennies. The children live with their mother, Katie, and their father, Johnny. Katie works hard as a janitor to help support the family, and Johnny is a singing waiter, who also drinks too much. The family is Catholic, and religion is an important focus in their lives. The family is poor, but they love one another and work hard to survive on very little.
Book II is a flashback that tells the story of Katie and Johnny's meeting, their courtship, and the early days of their marriage. The young family struggles to survive, and they are always short of money. Their lives are simple, their meals not elaborate, and their apartment clean but unadorned. Katie comes from a family of strong women, but Johnny is derived of weaker stock, and as the narrator makes clear, destined to die young.
Book III relates to Francie's and Neeley's experiences in school. Francie looks forward to school but soon discovers that the teachers in her school are unkind and often cruel to the poorest children. One day, Francie discovers a school that looks nicer and more pleasing to her, and once she is enrolled, Francie discovers that the new school is everything she had hoped it would be. Francie does well in her classes, especially in her English class.
The family celebrates many holidays together, and each one is marked by special traditions that the children enjoy. Christmas is an especially important holiday. The gifts are small, but the family does not expect more. One Christmas, as Francie and Neeley drag a Christmas tree up the stairs to their apartment, Katie thinks about the struggle the children have endured and becomes convinced that education will be the best way for the children to escape the poverty they are enduring.
Francie learns that women can be very cruel to one another, especially when they think another woman has violated sexual customs. Francie also has a close call when a rapist-murderer tries to attack her.
For most of her childhood, Francie overlooked her father's drinking because she loved him so much. She still loves him, but now that she is a teenager, she understands the economic cost of her father's drinking. Johnny's death when she is fourteen hits Francie especially hard. Katie is pregnant with their third child when Johnny dies. The next several months are a struggle for the family, but Katie vows to keep Francie and Neeley in school so that they can graduate in June. The new baby, Annie Laurie, is born in May, and Francie and Neeley graduate from eighth grade in June.
In Book IV, Francie begins working after graduation to help the family survive, since Katie cannot work as much with the new baby. Francie is quickly promoted and given large raises. When it is time to enroll in high school, Katie decides the Neeley will go to high school, while Francie will work to help support the family. Francie and Katie argue over this decision, and while Francie eventually agrees to do as her mother wishes, the argument creates a fissure in their relationship. The family is, however, economically more stable thanks to Francie's job.
Although she never gets the opportunity to go to high school, a life-time of reading has provided its own education. As a result, Francie takes summer college classes, where she meets Ben Blake, a fellow student who helps her study. Francie also meets Lee Rhynor, a young soldier due to ship overseas in a couple of days. Francie falls in love with Lee, but he returns to his hometown and marries his fiancée.
Sergeant McShane, a retired policeman who is now a successful politician, asks Katie to marry him. He will adopt baby Laurie and pay for Francie's and Neeley's college education. He is a kind and generous man, and while he can never take Johnny's place for Francie, he will make Katie happy and give her and Laurie easier lives.
In Book V, the family prepares to move from their old apartment the day before the wedding. Francie prepares to move to Wisconsin to attend college and walks the neighborhood, saying goodbye to all that is familiar to her. Ben has plans to attend college and law school, has given her a ring, and is willing to wait until Francie is sure that she loves him. The Tree of Heaven in the building courtyard, which symbolizes the strength and tenacity of the poor, continues to survive, just as the people survive.