In 1963, her first brush with notoriety came through Julian Wasser's iconic photograph of a nude, 20-year-old Babitz playing chess with the pioneering Dada artist Marcel Duchamp on the occasion of his landmark retrospective at the Pasadena Art Museum. The show was curated by Ferus Gallery's Walter Hopps, with whom Babitz was having an affair at the time. The photograph is described by the Smithsonian Archives of American Art as being "among the key documentary images of American modern art".

Babitz began her independent career as an artist, working in the music industry for Ahmet Ertegun at Atlantic Record, creating album covers. In the late 1960s, she designed album covers for Linda Ronstadt, The Byrds and Buffalo Springfield. Her most famous cover was a collage for the 1967 album Buffalo Springfield Again.