Born in Winschoten, he studied law at the University of Groningen. After his studies he began a career in the banking sector. In 1935, he became director of Heineken, the famous beer company. He held this post until 1948.
In 1945, he was among the organizers of the Stichting van de Arbeid, thus helping to lay the foundation of the post-war collective bargaining economy in The Netherlands.
Stikker entered politics in 1945, when he was elected to the First Chamber of the States General (the Dutch Senate). On March 23, 1946, he co-founded the Partij van de Vrijheid (PvdV, Freedom Party), together with some former members of the pre-war Liberale Staatspartij (LSP, Liberal State Party). On January 24, 1948, the PvdV was absorbed by the Volkspartij voor Vrijheid en Democratie (VVD, Popular Party for Freedom and Democracy), which is until today The Netherlands' most important Liberal party. Dirk Stikker was its first chairman (January 24 1948 - August 1948).
In 1948, Stikker became minister of Foreign Affairs in the first government led by Willem Drees (August 7, 1948 - March 15, 1951). After his own party had adopted a no-confidence motion over the government's colonial policy in New Guinea, Stikker resigned on January 23, 1951, prompting the cabinet's fall. He nevertheless returned as minister of Foreign Affairs in the second Drees cabinet (March 15, 1951 - September 2, 1952).
During Stikker's time in office as minister of Foreign Affairs, The Netherlands played an important role in the creation of NATO and the European Coal and Steel Community.
After his ministerial office, Stikker subsequently was Ambassador in London (1952 - 1958) and head of the Dutch Permanent Representation to the North Atlantic council and to the Organization for European Economy Co-operation, the predecessor of the OECD (1958 - 1961). On April 21, 1961, he succeeded Paul-Henri Spaak as NATO Secretary General. He resigned because of ill health on August 1, 1964, and was succeeded by Manlio Brosio.
In 1964, Dirk Stikker was awarded a honorary doctorate by Brown University (Providence, RI). He died in Wassenaar in 1979, aged 81.