Daughter of a French civil servant, she studied at the School of Higher Commercial Studies, earning a doctorate in demography, and in 1959 married Jacques Cresson, an executive with the automaker Peugeot. She joined the Socialist Party in 1965 and worked vigorously in François Mitterrand's (Mitterrand, François) failed presidential campaign of that year. She ran unsuccessfully for a parliamentary seat in 1975 but was subsequently elected mayor of Thuré (1977), member of the European Parliament (1979–81), and mayor of Châtellerault (1983). After Mitterrand's election to the presidency in 1981, Cresson served in a number of ministries—agriculture, tourism and foreign trade, industry and foreign trade, and European affairs—and became known for her outspokenness and combativeness.

In 1986 Cresson was elected as a Socialist deputy from Vienne. When Michel Rocard (Rocard, Michel) resigned the French premiership in 1991, her friend Mitterrand appointed her premier. She sought to improve France's industrial competitiveness while reducing social inequities. Rising unemployment and declining support for the Socialist Party among the voters prompted Mitterrand to replace Cresson as premier after she had been in office less than a year, however. In 1995 Mitterrand appointed Cresson to serve as European commissioner for science, research, and education. Some of her subsequent decisions elicited controversy and criticism, as did her inaction to correct known financial irregularities. Cresson and the entire European Commission resigned in 1999 because of alleged fraud and corruption. Charges were later brought against Cresson in 2003, although they were reduced the following year. In 2006 she was found guilty of favouritism and misconduct; however, no penalty or punishment was decreed.