A practitioner of Realpolitik, Kissinger played a prominent role in United States foreign policy between 1969 and 1977. During this period, he pioneered the policy of détente with the Soviet Union, orchestrated the opening of relations with the People's Republic of China, engaged in what became known as shuttle diplomacy in the Middle East to end the Yom Kippur War, and negotiated the Paris Peace Accords, ending American involvement in the Vietnam War. Kissinger has also been associated with such controversial policies as U.S. involvement in the 1973 Chilean military coup, a "green light" to Argentina's military junta for their Dirty War, and U.S. support for Pakistan during the Bangladesh War despite the genocide being perpetrated by his allies. After leaving government, he formed Kissinger Associates, an international geopolitical consulting firm. Kissinger has written over one dozen books on diplomatic history and international relations.

Kissinger remains widely regarded as a controversial figure in American politics, and has been condemned as a war criminal by journalists, political activists, and human rights lawyers. According to a 2014 survey by Foreign Policy magazine 32.21% of "America's top International Relations scholars" considered Henry Kissinger the most effective U.S. Secretary of State since 1965.

Kissinger remained at Harvard as a member of the faculty in the Department of Government and, with Robert R. Bowie, co-founded the Center for International Affairs in 1958 where he served as associate director. In 1955, he was a consultant to the National Security Council's Operations Coordinating Board. During 1955 and 1956, he was also study director in nuclear weapons and foreign policy at the Council on Foreign Relations. He released his book Nuclear Weapons and Foreign Policy the following year. From 1956 to 1958 he worked for the Rockefeller Brothers Fund as director of its Special Studies Project. He was director of the Harvard Defense Studies Program between 1958 and 1971. He was also director of the Harvard International Seminar between 1951 and 1971. Outside of academia, he served as a consultant to several government agencies and think tanks, including the Operations Research Office, the Arms Control and Disarmament Agency, Department of State, and the RAND Corporation.

Keen to have a greater influence on U.S. foreign policy, Kissinger became foreign policy advisor to the presidential campaigns of Nelson Rockefeller, supporting his bids for the Republican nomination in 1960, 1964, and 1968. After Richard Nixon became president in 1968, Kissinger was appointed as National Security Advisor.

In December 2016, Kissinger advised then President-elect Donald Trump to accept "Crimea as a part of Russia" in an attempt to secure a rapprochement between the United States and Russia, whose relations soured as a result of the Crimean crisis.