O'Keeffe was born near Sun Prairie, Wisconsin. In 1905, O'Keeffe enrolled at the School of the Art Institute of Chicago. In 1907, she attended the Art Students League in New York City, where she studied under William Merritt Chase. In 1908, she won the League's William Merritt Chase still-life prize for her oil painting "Mona Shehab" (Dead Rabbit with Copper Pot). Her prize was a scholarship to attend the League's outdoor summer school at Lake George, New York. While in the city in 1908, O'Keeffe attended an exhibition of Rodin's watercolors at the 291 Art Gallery, owned by her future husband, photographer Alfred Stieglitz.
O'Keeffe abandoned the idea of pursuing a career as an artist in the fall of 1908 claiming that she could never distinguish herself as an artist within the mimetic tradition, which had formed the basis of her art training, and she took a job in Chicago as a commercial artist. During this period, she did not paint and said that the smell of turpentine made her sick. She was inspired to paint again in 1912, when she attended a class at the University of Virginia Summer School, where she was introduced to the innovative ideas of Arthur Wesley Dow, who encouraged artists to express themselves using line, color, and notan (Japanese system of lights and darks) harmoniously.
O'Keeffe first came to the attention of the New York art community in 1916, several decades after women had gained access to art training in America's colleges and universities, and before any of its women artists were well known or highly celebrated. Within a decade, she had distinguished herself as one of America's most important modern artists, a position she maintained throughout her life. As a result, O’Keeffe not only carved out a significant place for women painters in an area of the American art community that had been exclusive to men, but also she had become one of America's most celebrated cultural icons well before her death at age 98.
Her abstract imagery of the 1910s and early 1920s is among the most innovative of any work produced in the period by American artists. She revolutionized the tradition of flower painting in the 1920s by making large-format paintings of enlarged blossoms, presenting them close up as if seen through a magnifying lens. And her depictions of New York buildings, most of which date from the same decade, have been recognized as among the most compelling of any paintings of the modern city. Beginning in 1929, when she first began working part of the year in Northern New Mexico, which she made her permanent home in 1949, O’Keeffe depicted subjects specific to that area. Through paintings of its unique landscape configurations, adobe churches, cultural objects, and the bones and rocks she collected from the desert floor, she ultimately laid claim to this area of the American Southwest, which earlier had been celebrated primarily by male artists; the area around where she worked and lived has become known as “O’Keeffe Country."
O'Keeffe became increasingly frail in her late 90s. She moved to Santa Fe in 1984, where she died on March 6, 1986, at the age of 98. In accordance with her wishes, she was cremated and her ashes were scattered to the wind at the top of the Pedernal Mountain, over her beloved "faraway".