O'Keefe was born in 1887 in Sun Prairie, Wisconsin. She later studied at the Art Institute of Chicago and worked briefly as a commercial artist.
After spending her early years in Chicago and New York, O'Keefe moved west to Texas in 1912 and later to New Mexico in 1946. She died at the age of 99 on March 6, 1986.
O'Keefe lived in New York briefly before moving to Texas to work as an art supervisor in the public schools of Amarillo and later as a department head at West Texas State College. Later, O'Keefe became interested in the natural beauty of New Mexico, eventually purchasing an adobe home there.
O'Keefe married New York photographer Alfred Stieglitz in 1924. She studied art under noted painter William Merritt Chase and learned about art education from Columbia University's Arthur Wesley Dow.
O'Keefe's incredible paintings have come to represent the beauty of the American West. With a fondness for creating paintings on a large scale, her work is known for its unusual and sometimes startling points of view.
Some experts contend that O'Keefe's paintings carried an underlying theme of sexuality. O'Keefe always denied such assertions
O'Keefe's beloved adobe home in New Mexico was featured in a number of her paintings.