O'Keeffe was born on November 15, 1887, in a farmhouse located at 2405 Hwy T in the town of Sun Prairie, Wisconsin. Her parents, Francis Calyxtus O'Keeffe and Ida (Totto) O'Keeffe, were dairy farmers. Her father was of Irish descent. Her maternal grandfather George Victor Totto, for whom O'Keeffe was named, was a Hungarian count who came to the United States in 1848.

O'Keeffe was a legend beginning in the 1920s, known as much for her independent spirit and female role model, as for her dramatic and innovative works of art. Nancy and Jules Heller said, "The most remarkable thing about O'Keefe was the audacity and uniqueness of her early work." At that time, even in Europe, there were few arts exploring abstraction. Even though her works may show elements of different modernist movements, such as Surrealism and Precisionism, her work is uniquely her own style. She received unprecedented acceptance as a woman artist from the fine art world due to her powerful graphic images and within a decade of moving to New York City, she was the highest paid American woman artist. She was known for a distinctive style in all aspects of her life. O'Keeffe was also known for her relationship with Stieglitz, in which she provided some insight in her autobiography.  A substantial part of her estate's assets were transferred to the Georgia O'Keeffe Foundation, a nonprofit. The Georgia O'Keeffe Museum opened in Santa Fe in 1997. The assets included a large body of her work, photographs, archival materials, and her Abiquiu house, library, and property. The Georgia O'Keeffe Home and Studio in Abiquiu was designated a National Historic Landmark in 1998 and is now owned by the Georgia O'Keeffe Museum.  In 1996, the U.S. Postal Service issued a 32 cent stamp honoring O'Keeffe. In 2013, on the 100th anniversary of the Armory Show, the USPS issued a stamp featuring O'Keeffe's Black Mesa Landscape, New Mexico/Out Back of Marie's II, 1930 as part of their Modern Art in America series.  A fossilized species of archosaur was named Effigia okeeffeae ("O'Keeffe's Ghost") in January 2006, "in honor of Georgia O'Keeffe for her numerous paintings of the badlands at Ghost Ranch and her interest in the Coelophysis Quarry when it was discovered".  O'Keeffe holds the record ($44.4 million in 2014) for the highest price paid for a painting by a woman.

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