Aubry joined the PS in 1974 and was appointed Minister of Labour by Prime Minister Édith Cresson in 1991, but lost her position in 1993 after the Right won the legislative elections. However, she became Minister of Social Affairs when Lionel Jospin was appointed Prime Minister in 1997. She is mostly known for having pushed the controversial 35-hour workweek law, known as the "Loi Aubry", reducing the nominal length of the normal full-time working week from 39 to 35 hours.

Aubry stepped down from her Cabinet post in 2001 to be elected Mayor of Lille in place of Pierre Mauroy. Aubry subsequently lost her seat in the National Assembly in the general election of 2002. In March 2008, she was reelected Mayor of Lille, with 66.55% of the votes.

In November 2008, she was elected to lead the Socialist Party, narrowly defeating Ségolène Royal; while Royal disputed the results, the Socialist Party declared on November 25, 2008 that Aubry had won the contested election.

With Dominique Strauss-Kahn, Aubry is seen as a frontrunner for the Socialist presidential nomination for the 2012.

Aubry is the daughter of French Minister of Finance (1981–1985) and European Commission President (1985–1995) Jacques Delors.

Aubry was educated at the lycée Notre-Dame-des-Oiseaux and the lycée Paul-Valéry (in Paris) ; she holds a degree in economic science from the Pantheon-Assas Paris II University, a diploma from the Institut des Sciences Sociales du Travail, and one from the Institut d'Études Politiques de Paris in 1972.

Between 1973 and 1975, she studied at the École nationale d'administration (ÉNA, National School of Administration). She became a civil administrator at the Minister of Social Affairs (France) (Ministère du Travail et des Affaires sociales), during which time she was active within the French Democratic Confederation of Labour (CFDT). She became a professor at ÉNA in 1978, and was seconded to the State Council between 1980 and 1981.

Following the election of François Mitterrand to the French presidency in 1981, she was successively held several posts at the Ministry of Social Affairs, in the cabinets of Jean Auroux and Pierre Bérégovoy. In 1984, she investigated French asbestos policy for the Comité Permanent Amiante (Permanent Asbestos Committee, an informal public-private working group formed to manage the health problems of workers affected by asbestos). The group's deputy director, Jean-Luc Pasquier, testified before the courts to account for the group's members' actions.

After the defeat of the socialists in the French legislative election of 1986, she was named Master of Requests at the State Council. From 1989 to 1991, she took up the post of Assistant Director at Pechiney, working with Jean Gandois. She was involved with the opening of a plant at Dunkerque and the closure of the aluminium works at Noguères.

Aubry was named Minister of Labour, Employment and Vocational Training by Édith Cresson, and carried on in this capacity in the Bérégovoy ministry until March 1993. According to Jean-Luc Pasquier, she supported the controlled use of asbestos whilst all other members of the EEC supported an outright ban, thus effectively vetoing a European decree against asbestos. France did not ban asbestos until 1997. In January 2010, a public health judge charged with investigating former government measures on asbestos had Aubry interrogated by gendarmes in Lille.