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Reilly was born in The Bronx, New York City, New York, United States, North America, the son of Charles Joseph Reilly, an Irish Catholic commercial artist, and Signe Elvera Nelson, a Swedish Lutheran. When young, he would often make his own puppet theater to amuse himself. His mother, foreshadowing his future as an entertainer, often would tell him to "save it for the stage". At age 13, he survived the 1944 Hartford Circus Fire, which killed 169 people in Connecticut.

From 1976 on, Reilly primarily taught acting and directing for television and theater, including directing Julie Harris (with whom he had acted in Skyscraper in 1965-66), who was portraying Emily Dickinson in her one-woman Broadway play The Belle of Amherst, by William Luce. In 1979, he directed Ira Levin's play Break a Leg on Broadway. Despite the previous year's success of Levin's Deathtrap, Break a Leg closed after one performance. Reilly earned a 1997 Tony Award nomination as Best Director of a Play for the revival of The Gin Game, starring Julie Harris.  In 1990, he directed episodes of Evening Shade. Reilly also made guest appearances in the 1990s on The Drew Carey Show, The Larry Sanders Show, Family Matters, Second Noah, and as eccentric writer Jose Chung in the television series The X-Files ("Jose Chung's From Outer Space"), Millennium ("Jose Chung's Doomsday Defense"), and occasionally as the voice of "The Dirty Bubble" in the animated series SpongeBob SquarePants, before he was replaced by Tom Kenny. Reilly was nominated for Emmy Awards in 1998 and 1999 for his performances in The Drew Carey Show and Millennium, respectively.  Reilly was a longtime teacher of acting at HB Studio, the acting studio founded by Herbert Berghof and made famous by Berghof and his wife, the renowned stage actress Uta Hagen. His acting students included Lily Tomlin, Bette Midler, and Gary Burghoff.  Reilly had a voice role in three films by Don Bluth: All Dogs Go to Heaven as Killer in 1989, Rock-a-Doodle as Hunch in 1991, and A Troll in Central Park as King Llort in 1994. In each one, he played the villain's dim-witted sidekick.
Charles Nelson Reilly