Born in Liège in a Protestant family, he studied law at the University of Liège, where he obtained a PhD in 1926. He began his career as a barrister at the Court of Appeal in Liège. His commitment to the Walloon movement drew him into politics. He joined the Liberal party and was elected city councillor of Liège in 1935. In 1939, he won a seat in the Chamber of Representatives.
In the wake of World War II, he was one of the most vocal opponents of the policy of "independence" (in fact, neutrality) of the Belgian government and Leopold III. Mobilized as reserve officer in 1940, he was captured by the Germans and spent the rest of the war in captivity.
After the war, he became an advocate of the federalization of Belgium. As early as 1947, he promoted a bill on the organization of a federal state. However, a majority in the Belgian Parliament refused to take it into consideration.
Rey was Minister of Reconstruction from 1949 until 1950, and Minister of Economy from 1954 until 1958. As such, he was involved both in the early development of the European Coal and Steel Community and in the negotiations that led to the creation of the European Economic Community (EEC) and the European Atomic Energy Community (EAEC).
Member of the Commission of the CEE from 1958 until 1967, responsible for external relations, he played an important role in the negotiations of the Kennedy Round (1964 – 1967).
In 1967, he succeeded Walter Hallstein as President of the European Commission (he was the first President of the Commission of the merged CSCE, CEE and EAEC). Still a convinced federalist, he undertook to reinforce the Community institutions. He won increased powers for the European Parliament and advocated its election by universal suffrage. During his presidency, he oversaw the completion of the customs union (1968).
He also played an important role the Summit of The Hague in 1969, where the European leaders decided to relaunch European integration with two new initiatives: on the one hand, Economic and Monetary Union (EMU), and on the other hand, European Political Cooperation (EPC), which foreshadow the euro and the Common Foreign and Security Policy of the European Union today. It was also at The Hague that France gave up its resistance against the accession of the United Kingdom to the EEC.
Finally, in 1970, the last year of this mandate, Rey managed to win the European governments' support for his proposal to give the Community "own resources". This meant that the EEC no longer depended exclusively on contributions by the member states, but could complete these with revenues from customs duties, levies on agricultural products from outside the Community, in addition to a share of the VAT revenue.
From 1964 until 1974, Rey was chairman of the board of the College of Europe in Brugge. He presided the over European Movement from 1974 to 1978 and was member of the Jean Monnet Foundation for Europe. In 1979, he became member of the first European Parliament elected by universal suffrage.
Jean Rey also remained active in Belgian politics. He became the éminence grise of the French-speaking liberals who broke away from the unitary Liberal party to form the Parti Réformateur et Libéral Wallon (PRLW) in 1976.
Jean Rey died in his native city Liège.