Hughes was born in Bedford Hills, NY, on July 16, 1915. He held jobs as a dock checker in New York harbor, a Macy's salesman and a Wall Street copyreader before auditioning for the stage on a dare from a friend. His career, which began in 1934 with one line in the Shakespeare Fellowship Repertory Company production of The Taming of the Shrew, spanned seven decades. Hughes made his Broadway debut in 1935 in Herself Mrs. Patrick Crowley. He then toured the United States performing in stock theatrical shows before serving in World War II. By 1945, he was back in America on the stage. While performing in a veterans' hospital show, he met actress Helen Stenborg, his wife of 56 years, whom he married in 1950.
Hughes also had a long history on the small and big screens. His film credits include Hamlet with Richard Burton, Midnight Cowboy, The Hospital, Cold Turkey, Where's Poppa?, First Monday in October, Oh, God!, Tron, Maxie, The Lost Boys, Doc Hollywood, Sister Act 2 and Cradle Will Rock. He starred in the television series Doc, Mr. Merlin and The Cavanaughs and played a recurring role on Blossom. In 1977, he won an Emmy Award for guest-starring on Lou Grant.
He served for over a decade as President of the Episcopal Actors' Guild and for many years on the council of The Actors' Fund. Hughes also held an honorary doctorate from Manhattan College, the school he'd dropped out of to become an actor.
Hughes is survived by his wife; his son, Tony Award-winning director Doug Hughes; his daughter, Laura Hughes; and a grandson, Samuel Hughes Rubin.