Neel grew up in Pennsylvania and enrolled at the Philadelphia School of Design for Women, where she was taught by Robert Henri of the Ashcan School. After marrying the Cuban painter Carlos Enríquez in 1925^[1], she moved to Havana and became involved with the Cuban Vanguardia movement. Their daughter Santillana died of diphtheria just before her first birthday. When Enríquez left for Paris in 1930 he took their second daughter, Isabetta, back to Cuba. Neel suffered a breakdown and attempted suicide, was hospitalised, and eventually returned to New York.

She supported herself through the Works Progress Administration under Roosevelt's New Deal and used the period to paint street scenes and the lives of working people. She deliberately moved to Spanish Harlem in order to connect with, as she put it, "real people." Her method was demanding: she made subjects sit for hours in silence, waiting for raw emotion to surface. "Even if I'm not working," she said, "I'm still analysing people. If I hadn't been an artist, I could have been a psychiatrist."

Her portrait of the poet Frank O'Hara (1960^[1], National Portrait Gallery, Smithsonian) is one of her most discussed works: a narrow vertical canvas at 86 x 41 cm in which the scale gives the figure an uneasy, compressed presence.