This groundbreaking historical novel follows several generations of an African American family, beginning with Kunta Kinte, a man captured in Gambia in the 18th century and sold into slavery in the United States. Through Kinte and his descendants, the narrative explores the brutal realities of slavery and its aftermath, the struggle for freedom and civil rights, and the perseverance of a family through immense hardship. The story is based on the author's own family history, making it a significant work in the exploration of African American heritage and identity.

Set in early 20th century Baltimore, the novel follows the life of Miss Susie Slagle, a boarding house owner who rents out rooms to medical students. The narrative is full of colorful characters, including the students themselves, who bring their own unique stories and perspectives. The book provides a vivid depiction of the time period, exploring topics such as gender roles, class distinctions, and the challenges and triumphs of pursuing a medical career.