The United States established diplomatic relations with South Africa in 1929, following the United Kingdom's recognition of South Africa's domestic and external autonomy within the British Empire. Until the 1990s, the South African Government followed a policy of white domination over the majority-black population, and racial separation (apartheid). From the 1970s through the early 1990s, U.S.-South Africa relations were severely affected by South Africa's racial policies.

Since the abolition of apartheid and 1994 democratic elections, the countries have enjoyed a solid bilateral relationship. South Africa is a strategic partner of the United States, particularly in the areas of security and trade. The two countries share development objectives throughout Africa, and South Africa plays a key economic and political role in the African continent. The United States seeks opportunities for increased U.S.-South African cooperation on regional and international issues. In 2010, the United States and South Africa launched a strategic dialogue aimed at deepening cooperation on the entire range of issues of mutual interest and/or concern.