Born Dorothea Cross in Lunenburg, Massachusetts on September 2, 1908, she attended Bryn Mawr College, where she studied chemistry and biology. She graduated in 1930, and went to work at the Johns Hopkins Hospital as a technician. After two years, she matriculated at the Johns Hopkins School of Medicine, and graduated with her Doctor of Medicine in 1936.
After earning her Doctor of Medicine, Leighton studied anthropology at Creighton University.
She was a resident physician in psychiatry at a clinic in Baltimore. In 1940, Leighton did fieldwork with Navajo people in Arizona and New Mexico, affiliated with the University of Chicago. In 1942, Leighton published a book that compared the Navajo philosophy of health with that of whites.
She then served as a physician with the Indian Personality Research Project from 1942–1945.
During this time, she worked with Clyde Kluckhohn and John Adair. Her 1944 book Navajo at the Door, with Alexander Leighton, is considered "the earliest example of applied medical anthropology".
She was a professor of child development and family relations at Cornell University from 1949 to 1952. While at Cornell, she studied psychiatry in a rural context, via fieldwork in Stirling County, Nova Scotia.
Around 1960, she traveled to Nigeria to do similar fieldwork with Yoruba people, and also did similar studies in Sweden.
Leighton then became a professor of public health and anthropology at the University of North Carolina, a position she held from 1965–1974, when she retired. She moved to Fresno, California, and continued to be somewhat involved in academia. In 1977, she was a lecturer at the University of California, San Francisco, and from 1981–1982 she was a visiting professor at the University of California, Berkeley, her last academic position before her death on August 15, 1989.
Leighton founded the Society for Medical Anthropology while a professor at the University of North Carolina.
She was its first president
