Born in Belfast, Northern Ireland, McGuinness was educated in Alexandra College, Trinity College Dublin and the King's Inns. In the 1960s she worked for the Labour Party. She was called to the Irish bar in 1977 at age 42. In 1989 she was called to the Inner Bar.
In 1979 she was elected as an independent candidate to Seanad Éireann at a by-election on 11 December 1979 in the Dublin University constituency following the resignation of Conor Cruise O'Brien, taking her seat in the 14th Seanad. She was re-elected at the 1981 elections to the 15th Seanad, and in 1983 to the 17th Seanad, where she served until 1987. She lost her seat to David Norris. She was appointed to the Council of State on 2 May 1988 by President Patrick Hillery and served until 1990.
She was appointed a judge in the Circuit Court in 1994, the first ever woman. In 1996 she was appointed to the High Court and remained there until her appointment to the Supreme Court in January 2000.
In November 2005 she was appointed Adjunct Professor at the Faculty of Law, National University of Ireland, Galway. She was also appointed President of the Law Reform Commission in 2005, and held that position until 2011.
In April 2009 she was awarded a "Lord Mayor's Award" by Dublin Lord Mayor Eibhlin Byrne "for her contribution to the lives of children and families in the city through her pioneering work". In September 2010 she was named as one of the "People of the Year" for "her pioneering, courageous and long-standing service to Irish society". In November 2012 she won the 'Irish Tatler Hall of Fame Award'
In addition to her judicial career, McGuinness has served on the Employment Equality Agency, Kilkenny Incest Investigation, the Forum for Peace and Reconciliation, the National Council of the Forum on End of Life in Ireland, and the Irish Universities Quality Board. In June 2011 she became patron of the Irish Refugee Council. In November 2011 she was appointed Chairperson of the "Campaign for Children"
She has received honorary doctorates from the University of Ulster, the National University of Ireland, the University of Dublin and the Higher Education and Training Awards Council (HETAC).
In February 2013 McGuinness accepted the Honorary Presidency of Trinity College Dublin's Free Legal Advice Centre
In January 2014 she was appointed by The Minister for Communications, Energy and Natural Resources, Pat Rabbitte to Chair the expert panel to oversee the preparation of reports on the best underground route options to compare with the Grid Link and Grid West high voltage power lines in Ireland.
In March 2015 she received an Alumni Award from Trinity College Dublin.
She was married to broadcaster and writer Proinsias Mac Aonghusa and has three children.
In November 2014 the Children's Rights Alliance established the Catherine McGuinness Fellowship on Children’s Rights and Child Law, a one-year Fellowship Programme for newly qualified barristers to work as part of their Legal and Policy Team on law and policy reform for children in the area of children's rights and child law in the Irish context. The Programme was developed in partnership with the Bar Council of Ireland and with the support of the Family Lawyers Association of Ireland.
The Fellowship was launched by the Chief Justice of Ireland, Susan Denham who described McGuinness as "an advocate at heart" and a "patriot, in the true sense of the word" who "stands up for the rights of others, particularly those who are marginalised and vulnerable in our society."