Born in DeKalb Illinois, Mr. Wirtz attended Beloit College and Harvard Law School. He was on the faculties of the University of Iowa and Northwestern University before serving during World War II with the War Labor Board. In 1946, he chaired the National Wage Stabilization Board. He then returned to teaching at Northwestern and in 1956 managed Adlai Stevenson's unsuccessful campaign for President against Dwight Eisenhower.

In 1961, he left a lucrative position with a Chicago law firm to join the Kennedy administration as undersecretary of Labor. President Kennedy promoted him to Secretary of Labor in 1962 after naming his predecessor Arthur Goldberg to the Supreme Court. Wirtz was to continue in that post after Johnson succeeded Kennedy in 1963 and stayed on until Johnson completed his second term in January 1969.

Wirtz himself said of his time as Secretary of Labor, "If there was a central unifying theme, it was in the insistence that wage earners - and those seeking that status - are people, human beings for whom 'work,' but not just 'labor' ... constitutes one of the potential ultimate satisfactions." He championed economic policies to maximize employment, even at the risk of higher inflation. Speaking of the unemployment problem, he told one interviewer in 1962 that "I think the situation is so deplorable in human terms that it warrants an indignant intolerance of any explanation for it in terms of any kind of economic analysis." At the end of his time in office he told reporters that he was most proud of the fact that the nation's unemployment rate had dropped during his tenure from 5.8% to 3.3%.

Under his leadership the Labor Department expanded job-training and education programs for the underemployed and at-risk youth, increased unemployment assistance for those who lost jobs to foreign trade, and created literacy programs for workers. Wirtz was also a leader in the passage of laws prohibiting discrimination in hiring or pay against women and older workers. He strictly enforced laws against racial discrimination in hiring and pay and publicly criticised construction unions for their bias against African-American workers. He was among the first to call for laws protecting workers with disabilities from discrimination. His investigation of working conditions among workers in the Bracero Program that since 1942 had brought temporary contract laborers from Mexico to work on American farms led to the termination of the highly exploitative program in 1964. Other major achievements included forestalling or ending several high-profile strikes, including a longshoremen's strike and another affecting New York City's newspapers.

In the Johnson administration, he played a major role in creating the programs and policies of LBJ's "War on Poverty." So much so that current Labor Secretary Hilda Solis has called him "President Johnson's general in the war on poverty." He was a vigorous advocate both of retraining for workers to cut unemployment and of legislation to root out causes of joblessness including remedial education for school dropouts. His close relationship with LBJ ended when he sent a note to the President expressing his doubts about the Vietnam War. "That was the end of the close relationship," he told National Public Radio in a 2008 interview, but he remained in the Cabinet till the end of Johnson's term.