In March 1972, Renfree finished her PhD, worked for six months in Zoology at ANU and then moved to the University of Tennessee to work with Joe Daniel.

Renfree moved back to Australia to take up a lecturer position in vertebrate biology at Murdoch University, Perth, WA in 1973.

Her two daughters, Tamsin and Kirsten were born in 1983 and 1986.

Renfree, in collaboration with David Parer and Liz Parer-Cook, participated in The Nature of Australia, a series by the Australian Broadcasting Corporation celebrating Australia's bicentenary in 1988.

In 1991, Renfree was appointed Chair of Zoology and Head of Department at Melbourne University, a position she held until 2003.

She became a Laureate Professor of the University in 2002, and in 2003 was awarded a Federation Fellowship.

In 2011, Renfree was one of the lead researchers on the first kangaroo genome sequencing project Renfree currently serves on the Prime Minister's Science Prizes Committee for Australia.

Renfree was awarded the Gottschalk Medal in 1980, the Mueller Medal in 1997.

She was elected a Fellow of the Australian Academy of Science in 1997.

She was awarded the Gold Conservation Medal of the Zoological Society of San Diego for 2000, the Commonwealth of Australia's Centenary Medal in 2003, and was made an Officer of the Order of Australia (AO) in 2013 "for distinguished service to biology, particularly through leadership in the research into marsupial reproduction, and to the scientific community".

In March 2019 Renfree was awarded the Carl G. Hartmann Award by the Society for the Study of Reproduction and in 2020 the Macfarlane Burnet Medal and Lecture by the Australian Academy of Science.

Renfree co-authored a paper "Hormones and the evolution of viviparity" with Amoroso in 1979.