Wolpe, who had been ill with a heart condition, died Tuesday at his home in Saugatuck, Mich., said Ken Brock, a former staff member.
Africa, Wolpe was a main sponsor of the Comprehensive Anti-Apartheid Act, which demanded the end of apartheid and mandated sanctions against South Africa for its system of white-minority rule.
The bill banned most new trade in South Africa and included the release of political prisoner Nelson Mandela as a condition for ending the restrictions. Mandela was freed in 1990 and when apartheid ended four years later, "he wanted to personally thank Howard for his efforts," Secretary of State Hillary Clinton said in a statement.
Wolpe served seven terms in Congress, from 1979 to 1992, and spent a decade as chairman of the Foreign Affairs subcommittee on Africa. He also helped author legislation to provide famine relief and development assistance to Africa.
As special envoy to Africa's Great Lakes Region under President Clinton, Wolpe supported peace talks that helped bring an end to long-standing civil wars in Burundi and the Democratic Republic of Congo, Secretary Clinton said in the statement.
Wolpe later served as director of the Africa program at the Woodrow Wilson International Center for Scholars in Washington, D.C.
While there he did "pioneering work on post-conflict reconstruction," making "a major contribution to the peace efforts in several countries emerging from ethnic conflict," Clinton said.
Howard Eliot Wolpe III was born Nov. 3, 1939, in Los Angeles and graduated from University High School in 1956.
He earned a bachelor's degree from Reed College in 1960 and a doctorate in political science from MIT in 1967. He began teaching at Western Michigan University and later taught at the University of Michigan and Michigan State University.
In the late 1970s, he was a member of Michigan's House of Representatives, and in 1994 ran for the state's governorship but lost to incumbent John Engler.
His first marriage ended in divorce.
In 1992, he married Judith Hollister, who drowned in 2006 in a swimming accident while vacationing with him on the Pacific coast of Guatemala. Wolpe was also caught in the undertow but managed to swim to shore.
He is survived by his wife of three years, Julianne Fletcher, and his son from his first marriage, Michael Wolpe of Los Angeles.