Powdermaker completed her PhD on leadership in "primitive" society in 1928. Like her contemporaries, Powdermaker sought to identify her anthropological work with a "primitive" people and spent ten months conducting fieldwork among the Lesu people of New Ireland in present-day Papua New Guinea. After returning to the United States, Powdermaker was given an appointment at the new, Rockefeller Foundation supported Yale Institute of Human Relations. Its director, Edward Sapir, encouraged her to apply ethnographic field methods to the study of communities in her own society. She conducted what was probably the first such anthropological study in an African American community in Indianola, Mississippi from 1932-1934. It resulted in After Freedom: A Cultural Study In the Deep South.
In 1950, Powdermaker published Hollywood, the Dream Factory, the first, and to date, the only substantial anthropological study of the American film industry.
Her final book, titled Stranger and Friend, The Way of an Anthropologist was finally published in 1966. It was a personal account of her anthropological career, from the beginning as a labor movement leader to her last field work in an African copper mining community.
In 1968, Hortense Powdermaker retired from Queens College, where she had founded the department of anthropology and sociology, and moved to Berkeley, where she remained engaged in ethnographic fieldwork. She died two years later of a heart attack. The building on the Queens College campus that houses the anthropology and sociology departments (along with other social science disciplines) is named in her honor.