Born in Highland Park, Illinois, and christened John Robert Rietz, Jr., Reed studied Shakespeare in college. He first gained fame in the early 1960s for his leading role on the drama The Defenders. After winning the role of Mike Brady on The Brady Bunch, he became unhappy with his part, feeling that acting in the often silly sitcom was beneath the serious Shakespearean training. He wanted out of the show but was under contract. As a result of his unhappiness with the show's content, he often got into arguments with the creator, Sherwood Schwartz. One such argument even resulted in his being completely written out of the show's final episode. He was happy when the show ended, but he did return for the Brady Bunch Variety Hour and the two made-for-TV movies that reunited the Brady cast. Despite his discontent with the show as whole, by most accounts he genuinely liked and was liked by his fellow cast members on The Brady Bunch.

After the end of the Brady Bunch in 1974 he made limited appearances as guest stars on other television shows and in made-for-tv movies, including Pray for the Wildcats (1974), The Boy in the Plastic Bubble (1976) and Roots (1977). He also guest starred on Wonder Woman playing the Falcon. He played the role of Dr. Adam Rose in the hospital drama Nurse, during the 1981-82 season.

Reed died from colorectal cancer caused by the presence of HIV (see article) in Pasadena, California at the age of 59. He is buried in Skokie, Illinois.

Like many gay actors then and now, Reed was secretive about his sexuality for the sake of his career.

In 1971, he was the defendant in Anglia TV v. Reed, which is an important case in English contract common law.