Miller was a basketball star at UCLA, where his father was a physical education instructor. In his senior year, while working as a furniture mover to pay for school, he was discovered on Sunset Boulevard by a Hollywood agent who signed him with MGM. His screen test was directed by George Cukor.
He became the first blond Tarzan in Tarzan, the Ape Man (1959), a cheapie/quickie which lifted most of its footage from earlier Johnny Weissmuller movies. He was recommended by someone else considered for the role, William Smith. MGM had him under contract for 20 months; in that time, he worked eight weeks as Tarzan.
After that, he did guest spots on a number of television series, such as Northwest Passage, a 1958-1959 adventure program on NBC co-starring Keith Larsen and Buddy Ebsen and on NBC's western series, Overland Trail, starring William Bendix and Doug McClure, and Laramie, co-starring John Smith and Robert Fuller. He also appeared on Have Gun-Will Travel, starring Richard Boone. From 1961-1964, Miller was a regular on Wagon Train in the role of the scout, Duke Shannon. In 1965-1966, after Wagon Train was cancelled, he starred on NBC as the husband of Juliet Prowse in the sitcom Mona McCluskey. He also appeared on the western series Gunsmoke as Lijah The Fugitive
Miller guest-starred on Gilligan's Island in 1964 as lost surfer Duke Williams in the episode “Big Man on Little Stick”, in 1967 as a method actor playing Tongo the Ape Man in the episode “Our Vines Have Tender Apes”, and in 1970 as "Moose" on "I Dream of Jeannie". He would also guest-star on another Sherwood Schwartz production, The Brady Bunch, in 1973 as Carol Brady's egomaniacal high-school boyfriend Tank Gates in the episode "Quarterback Sneak".
In 1968, Miller appeared as "Wyoming" Bill Kelso in the Peter Sellers movie The Party, which he remembers as the most fun part he ever did. He appeared in the Battlestar Galactica episode "The Gun on Ice Planet Zero" and the Buck Rogers in the 25th Century episode "The Dorian Secret". He also appeared as John Hays on "Hawaii Five-O" in the episode "Pray Love Remember, Pray Love Remember" in 1968. His character was a college boyfriend wrongly accused of murder.
Miller later appeared as an alien invader in the television miniseries V. All together, he starred in over 200 episodic television series. He played the Gorton's Fisherman in his yellow rain gear on TV commercials for 14 years.
Denny Miller wrote an autobiography titled "Didn't You Used To Be...What's His Name?" and a book about the obesity problem in the United States called "Toxic Waist?...Get To Know Sweat!". USA Book News selected this last book as a Finalist in the Health Category for "Best Books 2006".
Miller now lives with his wife, Nancy, in Las Vegas, Nevada, and teaches classes in relaxation.