Fossey trained to become an occupational therapist at San Jose State College and graduated in 1954. She worked in that field for several years at a children's hospital in Louisville, Kentucky. In 1963 she took a trip to eastern Africa, where she met the anthropologist Louis Leakey (Leakey, Louis S.B.) and had her first glimpse of mountain gorillas. She returned to the United States after her trip, but in 1966 Leakey persuaded her to go back to Africa to study the mountain gorilla in its natural habitat on a long-term basis. To this end, she established the Karisoke Research Centre in 1967 and began a hermitlike existence in Rwanda's Virunga Mountains, which was one of the last bastions of the endangered mountain gorilla. Through patient effort, Fossey was able to observe the animals and accustom them to her presence, and the data that she gathered greatly enlarged contemporary knowledge of the gorilla's habits, communication, and social structure.

Fossey left Africa in 1970 to complete work for a doctorate at the University of Cambridge in England. In 1974 she received her degree in zoology with the completion of her dissertation, “The Behavior of the Mountain Gorilla.” She returned to Rwanda with student volunteers who made broader kinds of research possible. Motivated by the killing of Digit, one of her favoured gorillas, Fossey generated international media coverage in 1978 in her battle against poachers.