Käsebier's career in art followed from her first career as a mother. After studying painting at Pratt Institute and opening a portrait studio in New York in 1897, she switched to photography, displaying the influence of her painting training in her Pictorialist style. Her family and friends posed for her most celebrated series of photographs on the subject of motherhood.
Käsebier exhibited her photographs in the Philadelphia Photographic Society exhibitions, and Alfred Stieglitz reproduced five of her images in his journal Camera Notes in 1899. The following year, along with Anne Brigman, Käsebier was one of the first two women to be elected to the British Linked Ring; two years later she became a founding member of Stieglitz's Photo-Secession group. Stieglitz continued to champion her by devoting the first issue of his second journal, Camera Work, to her images. Käsebier broke with Stieglitz and the Photo-Secession in 1912 but continued to photograph until she closed her studio in 1929.