Due to Hall's height, he was often cast in Monster roles. He made his acting debut in the 1979 horror film Prophecy. He appeared as the alien in the 1980 horror film Without Warning and as Gorvil in the 1982 television movie Mazes and Monsters. In 1985, he co-starred in the short-lived series Misfits of Science. He guest-starred on the sitcom Night Court as a huge but gentle mental patient who humorously towered over bailiff Bull Shannon, played by Richard Moll, who is 6 ft 8 in (2.03 m), and a fellow mental patient, played by James Cromwell, who is 6 ft 7 in (2.01 m). The next year, Hall portrayed yet another Monster in the horror film Monster in the Closet, followed by the role of Harry in Harry and the Hendersons.
In 1986, Hall was cast as the main antagonist in Predator, starring Arnold Schwarzenegger. During its developmental stages, the Predator was going to be played by Jean-Claude Van Damme, who played the Predator for the first few scenes, but was not billed in the end credits. The producers decided to recast the role with Hall so that the Predator could more convincingly dominate the film's human characters with its greater size. Hall would go on to reprise the role in the 1990 sequel.
Following his role in Predator, Hall appeared in the feature film Big Top Pee-wee (1988) and had a guest spot on Star Trek: The Next Generation; Hall had been one of the actors considered for the role of Geordi La Forge on the latter, before the role went to LeVar Burton. From 1989 to 1990, he had a recurring role on the NBC sitcom 227. In 1990, Hall reprised his role as Harry in the television series Harry and the Hendersons, based on the 1987 film of the same name. He died during the series' first season.
While working on the TV series Harry and the Hendersons, Hall announced that he had contracted HIV from a blood transfusion. He died from AIDS-related pneumonia on April 10, 1991, a month short of his 36th birthday.
Hall was posthumously inducted into the Penn Hills Hall of Fame as part of the inaugural class on May 8, 2009.
