From 1959 to 1962, he was Director of Jean-Marcel Jeanneney's staff, in the ministry of Industry and Trade. Then, in 1967, President Charles de Gaulle chose him as vice-president of the European Commission for Economic & Financial Affairs. He stayed in Brussels until January 1973, serving in the Rey, Malfatti and Mansholt Commissions. Having come back to France, he joined the cabinet as minister of the External Trade in January 1976.

Minister of Economy and Finance : 1976–1978.

At the head of the cabinet, he was faced with the conflict which divided the parliamentary majority between the "Giscardians" and the neo-Gaullist Rally for the Republic (RPR) led by his predecessor Jacques Chirac. The right majority unexpectedly won the 1978 legislative election.

On several occasions, Raymond Barre made remarks that were interpreted as antisemitic, or at least supportive of antisemitism. In 1980, when he was prime minister, a bombing was attempted against the Union Libérale Israélite de France, a synagogue in the rue Copernic, Paris; however the bomb detonated in the street when the Jews attending shabbat were inside the synagogue, and not when they were out; but as a result some non-Jewish bystanders were killed. Raymond Barre then famously denounced:

Member of the National Assembly of France for Rhône (department) : 1981–2002. Elected in 1981, reelected in 1986, 1988, 1993, 1997.

Member of the Urban Community of Lyon : 1995–2001.

After his departure from the head of the cabinet, he was elected deputy of Rhône département under the label of the Union for French Democracy (UDF). He held his parliamentary seat until 2002.

Barre retired from active politics in June 2002. He was being treated at a hospital for a heart condition since April 2007 when he died on 25 August 2007. He was survived by his wife and two sons.

Minister of Foreign Trade : January–August 1976.