In August 1929, during a dinner party in Paris, the 41-year-old Monnet met 22-year-old Italian Painter Silvia Giannini (17 August 1907 – 22 August 1982) who had recently married Francisco Giannini, an employee of Monnet when he was a representative in Italy. In April 1931, Silvia gave birth to a daughter, Anna, whose legal father was Giannini.

Monnet firmly believed that the only path to an Allied victory lay in combining the war efforts of Britain and France, and he reflected on a concept that would coordinate war resources. In 1914, young Monnet was allowed to meet French Premier René Viviani on this issue and he managed to convince the French government to agree with him, in principle. However, during the first two years of the war, Monnet did not have much success pressing for a better organization of the allied economic cooperation. It was not until two years later that stronger combines like the Wheat Executive (end of 1916) and the Allied Maritime Transport Council (end of 1917) were set into motion, adding to the overall war effort.

Due to his contributions to the war effort, Monnet, at the age of thirty-one, was named Deputy Secretary General of the League of Nations by French premier Georges Clemenceau and British statesman Arthur Balfour, upon the League's creation in 1919.

Soon disillusioned with the League because of its laborious and unanimous decision-making processes, Monnet resigned in 1923 and devoted himself to managing the family Business, which was experiencing difficulties. In 1925, Monnet moved to America to accept a partnership in Blair & Co., a New York bank which merged with Bank of America in 1929, forming Bancamerica-Blair Corporation which was owned by Transamerica Corporation. He returned to international politics and, as an international financier, proved to be instrumental to the economic recovery of several Central and Eastern European nations. He helped stabilise the Polish złoty in 1927 and the Romanian leu in 1928. In November 1932, the Chinese Minister of Finance invited Jean Monnet to act as chairman of an East-West non-political committee in China for the development of the Chinese economy where he lived until 1936. During his time in China, Monnet's task of partnering Chinese capital with foreign companies led to the formal inauguration of the Chinese Development Finance Corporation (CDFC) as well as the reorganization of the Chinese railroads.

Since divorce wasn't allowed in most European countries, Silvia and Jean Monnet met in Moscow. In 1934, he returned from China via the Trans-Siberian railway, she from Switzerland. He arranged for Silvia to obtain Soviet citizenship; she immediately divorced her husband and married Jean Monnet.

The custody of Anna was a problem; in 1935 Silvia took refuge with Anna in the Soviet consulate in Shanghai, where they were living at the time, because Francisco Giannini was trying to obtain custody of the child. The legal battle was decided in favour of Silvia in 1937 in New York, but the ruling wasn't recognized by some other countries. In 1941 Monnet and Silvia had another daughter, Marianne. The Monnet family returned to France in 1945 and, after the death of Francisco Giannini in 1974, the couple married canonically in the cathedral of Lourdes.

In December 1939, Monnet was sent to London to oversee the collectivization of the British and French war industries. His influence inspired Charles de Gaulle and Winston Churchill to agree on an Anglo-French union, in an attempt to rival the alliance between Germany and Italy.

In August 1940, he was sent to the United States by the British Government, as a member of the British Supply Council, to negotiate the purchase of war supplies. Soon after his arrival in Washington, D.C., he became an advisor to President Franklin D. Roosevelt. Convinced that America could serve as "the great arsenal of democracy", he persuaded the President to launch a massive arms production program, both as an economic stimulus and to supply the Allies with military resources. In 1941, Roosevelt, with Churchill's agreement, launched the Victory Program, which represented the involvement of the United States in the war effort. After the war, John Maynard Keynes, a British Economist, claimed that through his coordinating, Monnet had probably shortened World War II by a year.

In 1943, Monnet became a member of the National Liberation Committee, the French government of De Gaulle in exile in Algiers, designated Commissaire à l'Armement. During a meeting on 5 August of that year, Monnet declared to the Committee:

In 1945, Monnet proposed the Monnet Plan, also known as the "Theory of l'Engrenage" (not to be confused with the Schuman plan). It included taking control of the remaining German coal-producing areas and redirecting the production away from the German industry and into the French, thus permanently weakening Germany and raising the French economy considerably above its pre-war levels. The plan was adopted by Charles de Gaulle in early 1946.

In 1947 France removed the Saar from Germany, with U.S. support, and turned it into the Saar Protectorate, which was politically independent and under complete French economic control. The area returned to German political administration in 1957 (economic reunification would take many years longer), but France retained the right to mine from its coal mines until 1981. (See: The Europeanisation of the Saarland)

The Jean Monnet House is located in Houjarray, Yvelines, 80 kilometres (50 miles) outside Paris. This old farm became Jean Monnet’s property in 1945, upon his return to France. It is here that Jean Monnet and his advisors, in the last days of April 1950, drew up the historic declaration that Robert Schuman used to address Europe on 9 May 1950, proposing the creation of the CECA (European Coal and Steel Community) as well as creating the basis of the European Community. In his office, Robert Schuman, Walter Hallstein, Paul-Henri Spaak, Konrad Adenauer, René Pleven, Helmut Schmidt, and many others exchanged their views with Jean Monnet on our Common Future. On Sundays, he had friends passing by come to his house; among them were Dwight Eisenhower, George Ball, and Edward Heath. He liked fireside conversations with famous journalists such as Walter Lippman, Hubert Beuve-Méry, or his neighbour Pierre Viansson-Ponté. This house was also where Jean Monnet died on 16 March 1979. In 1982, even though the house had deteriorated because of a lack of upkeep, the European Parliament considered Monnet’s home to be a symbolic place loaded with memories, thus being Common heritage for Europeans. The Parliament acquired it and entrusted its reconstitution, management, and organization to the Jean Monnet Association. Since 2000, a multimedia conference room has welcomed bigger groups of visitors. The Jean Monnet Association team organizes about 250 conferences on European history and current events each year.

When Germany agreed to join the European Coal and Steel Community according to the Schuman Plan in 1951, the ongoing dismantling of German industry was halted and some of the restrictions on German industrial output were lifted. West Germany joined the ECSC, alongside Italy, Belgium, Luxembourg and the Netherlands, while Britain refused, on grounds of national sovereignty.

In 1952, Jean Monnet became the first President of the High Authority and with the opening of the Common market for coal under the ECSC in 1953, the last civilian production limitations placed on German industry were lifted, and the role of the IAR was taken over by the ECSC.

In 1953 Monnet was awarded the Karlspreis by the city of Aachen in recognition of his achievements.

In 1955, Monnet founded the Action Committee for the United States of Europe in order to revive European construction following the failure of the European Defence Community (EDC). It brought political parties and European trade unions together to become a driving force behind the initiatives which laid the foundation for the European Union as it eventually emerged: first the European Economic Community (EEC) (1958) (known commonly as the "Common Market"), which was established by the Treaty of Rome of 1957; later the European Community (1967) with its corresponding bodies, the European Commission and the European Council of Ministers, British membership in the Community (1973), the European Council (1974), the European Monetary System (1979), and the European Parliament (1979). This process reflected Monnet's belief in a gradualist approach for constructing European unity.

On 6 December 1963, Monnet was presented with the Presidential Medal of Freedom, with Special Distinction, by United States President Lyndon Johnson. In 1972, Queen Elizabeth II made him an honorary Companion of Honour.

He was the first to be bestowed Honorary Citizen of Europe by the European Council of the European Union, for extraordinary work to promote European cooperation on April 2, 1976. Following this he became the first person alive to be pictured on a German stamp who was not also a German head of state.

5 years later, in 1979, Jean Monnet died at the age of 90 in his home in Houjarray, Bazoches-sur-Guyonne, where he was writing his memoirs.

In 1988, by order of the President François Mitterrand, Jean Monnet's remains were transferred to the Panthéon of Paris.

In April 2011, to commemorate the 60th anniversary of the signing of the Treaty of Paris, a new documentary, "Jean Monnet: Father of Europe" was produced. The documentary includes interviews with colleagues of Monnet such as Georges Berthoin (fr), Max Kohnstamm and Jacques-René Rabier, as well as former member of the European Court of Justice David A.O. Edward of the United Kingdom.

Later that year, Monnet successfully negotiated the Blum–Byrnes agreement with the United States, which cleared France from a $2.8 billion debt (mostly World War I loans) and provided the country with an additional low-interest loan of $650 million. In return, France opened its cinemas to American movies.