Mary Lenihan was born on 31 May 1937 in Athlone, County Westmeath. She was the daughter of Patrick Lenihan, a Fianna Fáil TD. She was educated in Wicklow and University College Dublin and qualified as secondary school teacher. She worked in local politics between 1974 and 1987 when she served on Athlone Urban District Council. In the November 1982 general election she was elected as a Fianna Fáil TD for the Longford-Westmeath constituency.
Between 1987 and November 1991 she served as Minister for Education. O'Rourke and her brother, Brian Lenihan, became the first brother and sister to serve in the same cabinet. She was then appointed Minister for Health. In February 1992 she contested the leadership of Fianna Fáil along with Michael Woods and Albert Reynolds. When Reynolds became party leader O'Rourke was dropped from the cabinet. She was then appointed Minister for State at the Departments of Industry and Commerce, and later Enterprise and Employment. When Bertie Ahern became party leader in 1994 O'Rourke became deputy leader of Fianna Fáil.
Following Ahern's election as Taoiseach in June 1997 O'Rourke became Minister for Public Enterprise. She lost her Dáil seat in the 2002 general election. She is currently leader of the upper house of the Oireachtas - Seanad Éireann.