The youngest of five children of Kenneth James and Etta Belle (née Perry) Hamilton, Virginia grew up amid a large extended family in Yellow Springs, Ohio. The area has been home to her mother's family since the late 1850s, when her maternal grandfather, Levi Perry, was brought into the state as an infant via the Underground Railroad. Her family encouraged her to read and write widely. She received a full scholarship to Antioch College but later transferred to Ohio State University.
She met poet Arnold Adoff while living in New York City, and married him in 1960. The two later returned with their children to live on the farm where Hamilton was raised. Adoff supported the family by working as a teacher, so Hamilton spent her time writing and had two children.
Hamilton was awarded the Hans Christian Andersen Award for Writing (the highest international recognition bestowed on an author or illustrator of children's literature), a MacArthur Fellowship, the Laura Ingalls Wilder Award and the University of Southern Mississippi de Grummond Medal. In 1990 she received the Catholic Library Association’s Regina Medal, given annually "for continued, distinguished contribution to children’s literature".
Hamilton died of breast cancer on February 19, 2002, in Dayton, Ohio, aged 65. Three books have been published posthumously: Bruh Rabbit and the Tar Baby Girl (2003), Wee Winnie Witch's Skinny (2004), and Virginia Hamilton: Speeches, Essays, and Conversations, edited by Arnold Adoff and Kacy Cook (2010).
In 1979, the Supersisters trading card set was produced and distributed; one of the cards featured Hamilton's name and picture.
The Virginia Hamilton Conference on Multicultural Literature for Youth has been held at Kent State University each year since 1984.
To recognize an African American author, illustrator, or author/illustrator for a body of his or her published books for children and/or young adults who has made a significant and lasting literary contribution. The Award pays tribute to the late Virginia Hamilton and the quality and magnitude of her exemplary contributions through her literature and advocacy for children and youth, especially in her focus on African American life, history and consciousness.