Hughes began his political career as a member of the Maryland House of Delegates from 1955 to 1959, representing Caroline County. He was elected a member of the Maryland Senate in 1958 and served until 1970 for district 15, representing Caroline, Cecil, Kent, Queen Anne's, and Talbot counties. In 1971, Hughes was offered and accepted the position of Secretary of Transportation for the state. In May 1977, however, Hughes resigned from his position because of a disagreement in the State Department of Transportation regarding the award of a construction contract for a subway in Baltimore City. Hughes was elected governor in 1978 after defeating Lieutenant Governor Blair Lee III in the Democratic primary election, and Republican John Glenn Beall, Jr. in the general election. Among other things, Hughes was a strong advocate for the Chesapeake Bay. He signed into law such legislation as that approving the Chesapeake Bay Agreement, which set into motion efforts to restore the Bay and recover from excessive fishing. Also during his administration, Maryland initiated foreign trade with China. The Savings and Loan crisis, involving the failure of many savings and loan organizations across the United States, hit Maryland near the end of Hughes' tenure with the run at Old Court Savings and Loans, but nevertheless steps were taken to insure Maryland savings and loans organizations. Hughes served two terms, defeating Republican challenger Robert A. Pascal in 1982, and concluded his governorship in 1987. In 1986, Hughes and Congressman Michael D. Barnes both unsuccessfully sought the Democratic nomination for the United States Senate seat being vacated by Charles "Mac" Mathias. They lost to Barbara Mikulski, who went on to win the general election.
Later career
Hughes was a member of the Chesapeake Bay Trust from 1995 to 2003; a member of the Board of Regents of the University System of Maryland from 1996 to 2000; the chairman of the Blue Ribbon Citizens Pfiesteria Commission in 1997; the chairman of the Maryland Appellate Judicial Nominating Commission from 1999 to 2003; and a member of the Committee to Establish the Maryland Survivors Scholarship Fund from 2001 to 2002. Hughes was a member of the Advisory Committee for the Eastern Shore Land Conservancy's Board of Directors. Hughes published an autobiography in 2006. Harry Hughes died on March 13, 2019, aged 92.