William Willard Wirtz was born on March 14, 1912, in DeKalb, Illinois. Wirtz graduated from Harvard Law School in 1937 and went on to teach law at the University of Iowa and Northwestern University.

During the war, from 1942 to 1945, Wirtz served as member of the War Labor Board, earning a reputation as an able mediator of labor disputes. At war's end, Wirtz worked with the National Wage Stabilization Board, after which he continued to teach law at Northwestern University.

Illinois Governor Adlai E. Stevenson appointed Wirtz to the Illinois Liquor Control Commission in 1950, and the two men developed a close relationship; when Stevenson ran for President in 1956, Wirtz was a key aide. President John Kennedy named Wirtz undersecretary of labor in 1961, and in September 1962, he tapped Wirtz to succeed Arthur Goldberg as secretary of labor, following the latter's appointment to the Supreme Court.

Wirtz ran the Labor Department for remainder of Kennedy's presidency and throughout the entirety of the Johnson administration. As secretary of labor, Wirtz was personally involved in ending and preventing multiple strikes, including the New York City newspaper strike and the longshoremen's walkouts. He was also involved in controversial railroad negotiations, throwing his support behind a plan resembling compulsory arbitration.

Wirtz was a strong supporter of job retraining programs as a way to combat unemployment, proposing amendments to the Manpower Development and Retraining Act which allowed for more extensive training, including remedial reading and writing courses for high school dropouts. He also supported legislation on federal aid to education and Medicare, and expanded Social Security measures.

Despite his strong objections to the war in Vietnam, Wirtz remained a part of the Johnson team. As part of the Johnson administration, Wirtz sought to end the dependence of American fruit and vegetable farmers on Mexican migrant workers. After serving as secretary of labor for seven years, Wirtz went on to practice law in Washington, D.C.