Nell Irvin Painter was born in Houston, Texas, on August 2, 1942, but she moved with her family to Oakland, California, while she was still an infant. Her parents were Frank Edward Irvin, a chemistry professor, and Dona Lolita Irvin, a personnel officer. In 1965, she married Colin Painter, but they divorced a year later. In 1989, she married Glenn R. Shafer, a teacher at the University of Kansas. She became the stepmother of Richard and Dennis Shafer.

Painter attended the University of California at Berkeley, deciding to major in anthropology after spending the summer of 1962 in Kano, Nigeria, with her parents. As part of Project Crossroads Africa, she helped to build a school for the indigenous people. Painter returned to Africa after graduation, this time to Ghana, where she discovered a love for history. She attended the University of California, where she received a master's degree in history in 1967, and earned a PhDfrom Harvard in 1974. Painter's first teaching appointment came in 1964 from the Ghana Institute of Languages, where she was employed for a little over a year.

Painter's contribution to the historical depictions of black Americans throughout the Progressive and Reconstruction Eras in the United States have gained her widespread recognition. Two works in particular, Exodusters: Black Migration to Kansas After Reconstruction (1977), and The Narrative of Hosea Hudson: His Life as a Negro Communist in the South (1979), have drawn much attention. New York Times Book Review contributor Joe Klein has said that Painter "seems to have a knack for finding the more curious nooks and crannies of the black experience in America."

Painter has received various awards and fellowships throughout her career as a historian. She has been presented with the Candace Award, the National Coalition of 100 Black Women, and the Coretta Scott King Award from the American Association of University Women. She has been awarded fellowships from the American Council of Learned Societies, the Guggenheim Foundation, and the National Endowment for the Humanities. At Harvard University, she received the Radcliffe Institute Fellowship, and at the University of North Carolina at Chapel Hill, she was a fellow in American history through the National Humanities Center. She was also an assistant professor at the University of Pennsylvania, in Philadelphia, as well as an associate professor of American and Afro-American history.

In 2005, Painter published Creating Black Americans: African American History and Its Meanings, 1619 to the Present. It won the Gustavus Myers Center Outstanding Book Award in 2006. In her most recent book,The History of White People (2010), Painter examines how whiteness is socially constructed and is used as a "defining characteristic" of race. According to literary critic Anthony Pagden, The History of White People does not focus on the actual history of white people, but rather delves into discussing how "white people invented the concept of whiteness" (Contemporary Authors Online).

In regards to her writing process, Painter says, "My books begin with a puzzle I can't solve. For The History of White People,it was 'why are white people—white Americans—called 'Caucasian?' ...visual imagery turned out to carry a great deal of weight, as much as facts and events. Then I draft and revise and draft and revise and revise and revise and revise." Furthermore, Painter never ceases to be surprised as a writer, as shown when she says: "The most surprising thing I have learned as a writer is how tenacious established notions are, even in the face of sound scholarship. Even though The History of White People is all about ideas about the white races, reviewers and readers referring to it persist in discussing race as black" (Contemporary Authors Online).

Lastly, Painter gives a bit of advice to readers and writers alike by explaining that a writer should not be limited in what he or she chooses to write about and that she hopes her books enable readers to think critically. She says I hope "...my books would urge readers to think critically of the world and its past, not take utterance at face value. I wish also that my books would help dismantle the widespread assumption that the body of the author determines not only what she can know, but also what she should write about (Contemporary Authors Online).

According to her web site, Painter has a forthcoming publication through W.W. Norton Press called Personal Beauty: Biology or Culture? She currently teaches at Princeton University as an Edwards Professor of American History.