Naomi Wallace was born in 1960 in Prospect, Kentucky, to Henry F. Wallace, an international correspondent, and Sonja de Vries, a Dutch justice and human rights worker.

Wallace obtained a Bachelor of Arts degree from Hampshire College. She then received two master's degrees from the University of Iowa. Currently, she divides her time between Kentucky and the Yorkshire Dales in Northern England (UK), where she lives with her partner, Bruce McLeod, with whom she has three children.

Wallace has taught English literature, poetry and playwrighting at Yale University, UCLA, University of Iowa, Illinois State University, Merrimack College, Hampshire College, American University of Cairo, Vrije University of Amsterdam and other institutions. She has also worked with women in the criminal justice system, and is a member of SURJ, Showing up for Racial Justice.[3] She has been called "a dedicated advocate for justice and human rights in the U.S. and abroad, and Palestinian rights in the Middle East," and her writing described as "muscular, devastating, and unwavering."

In the mid-2000s, Wallace was briefly detained by Homeland Security after defying the ban on travel to Cuba.

In August 2016, Wallace announced that she will be one of the Freedom Riders on the upcoming Women's Boat to Gaza.