May O'Brien's long career as a teacher in Western Australia began at Mount Margaret Mission, where she had grown up. After twenty-five years of teaching in rural and suburban schools she was transferred from the classroom to the Aboriginal Education Branch as a consultant, whose task was to facilitate the establishment of Aboriginal committees on education throughout the state.
O'Brien's contribution to education, particularly to Aboriginal education, was acknowledged with a British Empire Medal in 1977. She was also the recipient of a Churchill fellowship in 1984 to study education programmes in other Western societies, with a view to enabling indigenous people to retain their own cultures while adjusting to mainstream culture. In 1985 O'Brien was appointed to the position of Superintendant of Aboriginal Education. O'Brien has also been involved with the Aboriginal Lands Trust in Western Australia. In 2009, part of her life story was featured in the National Museum of Australia's exhibition From Little Things Big Things Grow: Fighting For Indigenous Rights 1920-1970.
1998John Curtin MedalMay O'Brien taught in rural and metropolitan schools for over 25 years before establishing the Aboriginal Committees on Education in WA. She also played an instrumental role in setting up Curtin's Aboriginal bridging course, providing young Aboriginal people with the chance to receive a tertiary education.