He studied at the California School of Fine Arts and at Stanford University. His reading of symbolist literature, such as the works of Mallarmé, James Joyce, Edgar Allan Poe, and Octavio Paz, inspired his work in modernism.
His travels to Mexico inspired his work "Little Spanish Prison" from 1944.
He was the eldest son of Robert Burns Motherwell II and Margaret Hogan Motherwell. He had two children with his wife Helen Frankenthaler, whom he married in 1958.
He was influenced by the work of surrealist painter Max Ernst.