Mary Frances "Francie" Nolan is the protagonist. The novel begins when Francie is 11 years old. The rest of the novel tells of Francie's life until she goes to college at 17. Francie grows up in Brooklyn in the early twentieth century; her family is in constant poverty throughout most of the novel. Francie shares a great admiration for her father, Johnny Nolan, and wishes for an improved relationship with her mother, hardworking Katie Nolan, recognizing similar traits in her mother and herself that she believes are a barrier to true understanding. The story of Francie traces her individual desires, affections, and hostilities while growing up in an aggressive, individualistic, romantic, and ethnic family and neighborhood; more universally it represents the hopes of immigrants in the early twentieth century to rise above poverty through their children, whom they hope will receive "education" and take their place among true Americans. Francie is symbolized by the "Tree of Heaven" that flourishes under the most unlikely urban circumstances.
Katie Rommely Nolan is Francie's mother and the youngest of her parents' four daughters. She is a second-generation immigrant with an evil father and an angelic mother who emigrated from Austria. She married Johnny Nolan when she was only 17 years old. Katie is a hardworking, practical woman whose youthful romanticism has been replaced by a frigid realism that often prevents her from sympathizing with those who love her most. She runs her home in such a way that her children are able to enjoy their childhood despite their extreme poverty. Because Johnny is an alcoholic and can rarely hold down a job, Katie becomes the family breadwinner by cleaning apartment buildings. Johnny, however, is more attuned to Francie's hopes of graduating from high school and becoming a writer. As Francie matures and develops an inclination toward academia, Katie realizes she is more devoted to Neeley than to Francie. Katie becomes pregnant just before Johnny dies and survives on her own until she agrees to marry Sergeant Michael McShane, a pipe-smoking local policeman-turned-politician.
Sissy Rommely is Katie's oldest sister and one of Francie's three aunts. Because of her parents' immigration and lack of knowledge in their new environment, Sissy never goes to school and is therefore illiterate. Sissy is kind, compassionate and beautiful, and many men fall in love with her. She is first married at 14, but after being unable to have any live children with her husband, Sissy leaves him. She marries two more times without ever getting a divorce. In between marriages, Sissy has a number of lovers. She calls each of her husbands and lovers by the name "John" until her final husband, who insists that she properly divorce her second husband and demands to be called by his own name, Steve. Sissy has ten stillborn children, but adopts an immigrant girl's baby daughter born out of wedlock and eventually gives birth to a healthy son of her own.
Johnny Nolan is Francie's father. He is a second generation immigrant from Ireland. He has a protective mother and had three brothers, all of whom died young. Johnny marries Katie Rommely at nineteen. He is charismatic, a loving husband and father, loved dearly by his family but especially by Francie. He is, however, an alcoholic. When he does hold a job, Johnny works as a singing waiter. He has a beautiful voice, a talent that is greatly admired but that is largely wasted because of his reputation as an alcoholic. After Katie tells him that she is pregnant with their third child, he stops drinking and immediately falls into a deep depression that ends with his death from alcoholism-induced pneumonia. He is a dreamer, in sharp contrast to Katie, whose view of the world is realistic.
Cornelius "Neeley" Nolan is Francie's little brother. He is a year younger than Francie and is favored by his mother, Katie. Neeley is a normal child who is more widely accepted by the neighborhood children than Francie. He shows more emotion when his father dies than Francie, who reacts to the loss by becoming even more determined to get an education and rise above her mother's limited vision. Neeley refuses to follow the tradition of Nolan men and determines to never become an alcoholic. Like Francie, he feels that their childhood was pleasant despite their poverty.
Eva "Evy" Rommely Flittman is Katie's youngest sister and Francie's other aunt, playing a role more minor than Sissy's. While considered throughout most of the novel to be in less dire circumstances than Katie, Evy struggles with her lazy husband Willie, a milk-wagon driver. When Willie suffers an injury, Evy drives the route instead and proves surprisingly good at it, treating the horses much more kindly than Willie does. At the end of the novel, he leaves her to travel as a one-man band and she carries on without a husband. When McShane gives Katie $1,000 as a wedding present, she passes $200 on to Evy - the value of Willie's life insurance policy. Unlike Sissy, Evy has had only one marriage and is not assumed to be promiscuous. She has three children, a girl (Blossom), and two boys (Paul Jones and Willie, Jr.).
Eliza Rommely is Francie's third aunt that is only mentioned once. She became a nun because of her mother's love of the Catholic church. Francie only met her once and Eliza was the reason Francie didn't want to become a nun for her facial hair.
Thomas and Mary Rommely are the parents of Sissy, Eliza, Evy, and Katie; they emigrate to America from Austria just before Sissy is born. While Thomas hates America, enjoys tormenting Mary, and forbids the speaking of English at home, Mary patiently endures her hardships and serves as a moral/practical guide for her daughters. Mary cannot read or write English, but she encourages Katie to ensure that her children learn the language, and also to begin saving money so she can buy land someday. The Rommelys' second oldest daughter, Eliza, is mentioned only briefly; she becomes a nun and joins a convent.
Flossie Gaddis is one of the Nolans' neighbors, a single woman who scares men away as she constantly looks for new relationships. She keeps her right arm covered at all times to hide scars from a childhood accident with a tub of scalding water. She has a brother, Henny, who is dying of tuberculosis.
Lee Rhynor is Francie's first love, a soldier on leave who tries to manipulate Francie into sleeping with him after he wins over her heart. When Francie refuses, he goes back to his fiancee.
Ben Blake is a boy Francie befriends during her first summer of college classes. Ben is driven and determined. While he is the object of Francie's affection at first, she feels differently after falling in love with Lee. However, at the end of the novel, Francie goes to college with a promise ring from Ben and hope of a future with him.