Harris Wofford was born in New York City in 1926. While attending high school, he was inspired by Clarence Streit's plea for a world government to found the Student Federalists (). After attending the University of Chicago, he attended law school at Yale and Howard University. He served in the United States Army Air Forces during the Second World War.

He began his public service career as an attorney for the U.S. Commission on Civil Rights serving from 1954 to 1958. In 1959, he became a law professor at University of Notre Dame. He was an early supporter of the Civil Rights movement in the south in the late 1950s and became a friend and unofficial advisor to Martin Luther King, Jr..

Wofford's political career began in 1960 when he served as an advisor to the presidential campaign of John F. Kennedy. When King was imprisoned shortly before the election, Wofford persuaded Kennedy to call King's wife and offer his support -- a move that helped shift the African American vote decisively in Kennedy's favor and may have won him the election.

In 1961, Kennedy appointed him as a Special Assistant to the President on civil rights. He also served as chairman of the Subcabinet Group on Civil Rights. He was instrumental in the formation of the Peace Corps and served as the Peace Corps' special representative to Africa and director of operations in Ethiopia. He was appointed Associate Director of the Peace Corps in 1962 and held that position until 1966.

Wofford's book Of Kennedy and Kings details his years in the civil rights movement and the creation of the Peace Corps.

In 1966, Wofford left politics to become president of the State University of New York at Old Westbury. In 1970, he became president of Bryn Mawr College in Pennsylvania holding that post until 1978.

After spending seven years in private law practice and one year as state chairman of the Democratic Party, Wofford was appointed by Pennsylvania Governor Bob Casey as the state's Secretary of Labor and Industry in 1987.

On April 4, 1991, Pennsylvania's senior U.S. Senator, John Heinz, died in an aviation accident leaving his seat in the U.S. Senate open. By law, the Pennsylvania governor was required to appoint a replacement until a special election could be held for the seat. After considering several potential candidates, including Allentown, Pennsylvania, native Lee Iacocca who turned down the job, Governor Casey appointed Wofford to the seat on May 8, 1991.

In the special election to be held in November 1991, he faced Dick Thornburgh, the former Pennsylvania governor and U.S. Attorney General under Presidents Reagan and George H. W. Bush. He had begun the campaign so far behind in the polls, most pundits assumed he had no chance of winning. His eventual victory over the former governor by 10 oints surprised many. His campaign was run by Paul Begala and James Carville and their dramatic success brought them to national attention. The campaign was also a proving ground for many of the themes that would underlie Bill Clinton's 1992 victory such as the focus on the economy and health care. He was one of the top choices for the vice presidential nomination under Clinton.

Wofford lost his bid for re-election to Republican Congressman Rick Santorum (32 years his junior), in November, 1994, when many Democrats were ousted from both Houses of the United States Congress in the 1994 Republican landslide.

After his time in the Senate, Wofford served as Chief Executive Officer of the Corporation for National and Community Service (the federal agency that runs AmeriCorps and several other domestic volunteer programs), from 1995 to 2001. Since his retirement, he has taught at the University of Maryland, College Park and served on the boards of several charities and service organizations including America’s Promise, Youth Service America and the Points of Light Foundation. He was the recipient of the John W. Gardner Leadership Award in 2002. He is currently a senior fellow at the Case Foundation in Washington, D.C.