He acted in college productions at Loyola and met fellow student Dwayne Hickman, with whom he later co-starred in The Many Loves of Dobie Gillis.

While teaching at Corpus Christi in 1958, Denver was permitted to audition for a role on the sitcom The Many Loves of Dobie Gillis as a favor to his sister, who was a secretary on the production lot.

[4] Following the cancellation of Dobie Gillis, Denver landed the title role on the sitcom Gilligan's Island, which ran for three seasons (1964–67) on CBS, and became a staple of later syndication.

During the run, Denver privately went out of his way to help his co-stars who warmly appreciated his efforts, such as successfully demanding that Russell Johnson and Dawn Wells be included in the series' opening credits (which also included a nod to their respective characters in the opening theme song), and insisting that Wells get an equal share of the series' publicity with Tina Louise.

During the 1980s and 1992, he reprised the character of Gilligan for numerous cameo appearances, including episodes of ALF, Meego and Baywatch, and played a bartender in the film Back to the Beach (1987).

Credited as Robert Denver, he had a small role in the Jimmy Stewart film, Take Her, She's Mine (1963), playing a beatnik poet working at a coffee shop.

In 1983, he appeared in the television movie High School U.S.. His final role was a small part in the Frankie Avalon-Annette Funicello comedy Back to the Beach (1987).

[9] On February 7, 1971, Denver was arrested in Anderson, California for possession of marijuana and drug paraphernalia in his car and pleaded no contest for a reduced sentence of a $250 fine.

[10] In 1998, he was arrested for marijuana delivered to his home, originally saying that the delivery came from Dawn Wells, who played Mary Ann on Gilligan's Island, but he later refused to name her in court, testifying that "some crazy fan must have sent it."

[13] On September 2, 2005, he died at age 70 from complications, including pneumonia[14] following throat cancer surgery at Wake Forest University Baptist Medical Center in Winston-Salem, North Carolina.