Following the end of World War II, Queen Wilhelmina ordered a Recall of Parliament and Stikker became a Member of the Senate taking the place of the deceased Samuel van den Bergh, on 20 November 1945.

After election of 1948 the Leader of the People's Party for Freedom and Democracy and Parliamentary leader of the People's Party for Freedom and Democracy in the House of Representatives Pieter Oud opted to remain in the House of Representatives instead of accepting a ministerial post in the new Cabinet Drees–Van Schaik and endorsed Stikker who had been serving as the Deputy Leader as Minister of Foreign Affairs, taking office on 7 August 1948.

Stikker remained in active politics, he was appointed as the Ambassador of the Netherlands to the United Kingdom, serving from 10 September 1952 until 15 June 1958 when he was appointed as the Permanent Representative of the Netherlands to NATO and the OECD.

After election of 1948 the Leader of the People's Party for Freedom and Democracy and Parliamentary leader of the People's Party for Freedom and Democracy in the House of Representatives Pieter Oud opted to remain in the House of Representatives instead of accepting a ministerial post in the new Cabinet Drees–Van Schaik and endorsed Stikker who had been serving as the Deputy Leader as Minister of Foreign Affairs, taking office on 7 August 1948.

After his retirement, Stikker occupied numerous seats as a corporate director and nonprofit director for supervisory boards in the business and industry world and for supervisory boards for several international non-governmental organizations and research institutes (Unilever, Van Lanschot, Netherlands Atlantic Association, Carnegie Foundation, Trilateral Commission and the DSM Company) and as an advocate and lobbyist for European integration and serving on several commissions for the European Economic Community and state commissions on behalf of the Dutch government.

In 1948, Stikker became minister of foreign affairs in the first government led by Willem Drees, holding that position until 1951.

After his party adopted a no-confidence motion over the government's colonial policy in New Guinea, Stikker resigned on 23 January 1951, prompting the cabinet's fall.

The Netherlands played an important role in the creation of NATO and the European Coal and Steel Community during Stikker's time in office as minister of foreign affairs.

After his ministerial office, Stikker was ambassador to the United Kingdom (1952–1958) and head of the Dutch Permanent Representation to the North Atlantic Council and to the Organization for European Economic Co-operation, the predecessor of the OECD (1958–1961).