Raised in an artistic household in Sun Prairie, Wisconsin, Ida O'Keeffe inherited the rather unenviable position of being the younger sister of one of the most famous woman artists of all time. In addition to Georgia (1887-1986), both of Ida's grandmothers, Mary Catherine O'Keeffe and Isabel Wycoff, were artists.

Ida painted in oil and watercolor, and worked as a printmaker, primarily in monotypes. She spent the early part of her career teaching art in Virginia. Whether for practical reasons (the O'Keeffe family's financial situation was perpetually unstable) or patriotic zeal in the wake of World War I, she studied nursing, graduating from Mount Sinai Hospital in 1921.

Even as a nurse, Ida retained her artistic ties, serving as Taos Art Colony patron Mabel Dodge Luhan's private nurse during the summer of 1929. Eventually Ida gravitated back toward the art world, returning to Columbia University to obtain her M.A. in fine arts in 1932.

As Georgia O'Keeffe's biographer Laurie Lisle has observed, a high degree of sibling rivalry existed with in the O'Keeffe family, and "certainly her sisters got the emphatic message that Georgia wanted to be the only O'Keeffe who painted" [Portrait of an Artist: A Biography of Georgia O'Keeffe (1980), pp. 202-3]. Georgia viewed Ida as a serious competitive threat, even from the time they were youngsters, when the adults in the family thought Ida the more artistically talented of the two.

Although her brother-in-law Alfred Stieglitz was fond of Ida and held her work in high regard, Georgia forbade him from ever exhibiting Ida's work, effectively ensuring that Ida's artistic career would be a difficult one. For her part, Ida irritated Georgia by remarking every so often that "all she needed was her own Stieglitz to put her on the map as an artist."

Ida exhibited frequently throughout the 1930s, winning awards at major juried exhibitions including the Southern States Art League and the National Association of Women Painters and Sculptors, and had several well-reviewed solo exhibitions of her own in New York galleries, including the Delphic Studios in 1933 (where she exhibited alongside some of her grandmothers' works) and 1937, the Park Art Galleries in 1939, and the Argent Gallery in 1940.

Adept in several artistic mediums, Ida also created a mural, God's House, for the WPA, and published an illustrated book, Forest Indians, in 1938. Critics commented favorably on the "mood and atmosphere" of her monotypes and termed her flower paintings "especially expert" [Howard Devree, "A Reviewer's Notebook," New York Times, January 26, 1939 and April 28, 1940]. Ida frequently worked with the same subject matter in several different media, completing a monotype, then painting the same subject in oil, or vice versa.

Although O'Keeffe's career was overshadowed by that of her famous older sister during her lifetime (and perhaps more so after her death), she received much praise for her paintings and was the subject of a posthumous exhibition in Santa Fe in 1974.