She studied classics at the Institute of the Sisters of Saint Andrew in Charleroi, before going on to graduate in law from the Université Catholique de Louvain in 1984. In 1985, she took a Post Graduate Diploma in European Law at the Universiteit van Amsterdam (UvA).
She started her career at the Bar in Brussels. From 1995 to 1999 she was a delegate to the Belgian Senate. She has been the president of the CDH party since, and played a prominent role in the 2007-2008 formation negotiations for the Leterme I Government.
She was Deputy Prime Minister and Minister for Employment and Equal Opportunities in the Leterme I Government, which took office on 20 March 2008.
When the Leterme I government failed, Joëlle Milquet retained her seat on the Van Rompuy I Government, then on the Leterme II Government.
As of 2012, she is the Deputy Prime Minister, Minister of the Interior and for Equalities.