In the 1970s, she was an administrator at the Canadian Committee for Fertility Research in Montreal, and a lecturer at the Université de Montréal.
Pépin entered the House of Commons of Canada in the 1984 election when she became the Liberal Member of Parliament for Outremont, Quebec succeeding Marc Lalonde.
Some have suggested that she lost the ultra-conservative Hasidic vote, and thus the seat, because of her pro choice stance.
In 1997, she was appointed to the Senate of Canada on the recommendation of Prime Minister Jean Chrétien, and served as Speaker pro tempore of the Upper House from 2002 to 2004.
Until her retirement, she was a member of the Senate Standing Committee on Social Affairs, Science and Technology.