He made his screen debut in 1956 as the voice of Big Brother in Michael Anderson's film version of George Orwell's 1984 starring Edmond O'Brien. He returned to Canada afterwards and gained film experience appearing on the TV series Tugboat Annie and The Last of the Mohicans. Vernon typically played a stern, authoritarian kind of character. He made his Broadway debut in 1964 as DeSoto opposite Christopher Plummer and David Carradine in The Royal Hunt of the Sun. During the Golden Age of CBC Drama in the 1960s he co-starred in Edna O'Brien's A Cheap Bunch of Nice Flowers opposite Colleen Dewhurst, and opposite William Hutt and Rita Gam in Uncle Vanya. These prestige productions led to his starring in the CBC series Wojeck in the late 1960s, playing a crime-fighting medical examiner (the series has been acknowledged as the inspiration for the later American series Quincy M.E., later starring in as a gangster in the episode Requiem For The Living). He left the series in order to further his acting career in the United States. In 1967, he appeared opposite Lee Marvin in Point Blank.
In 1969, he played Cuban revolutionary Rico Parra in Alfred Hitchcock's Cold War era spy movie Topaz. After appearing in a string of television episodes and films, he became well known internationally for playing the by-the-book mayor of San Francisco perpetually frustrated by Clint Eastwood in the first Dirty Harry movie (a role he later parodied in the premiere episode of Sledge Hammer!). He also played the sympathetic Fletcher in Eastwood's The Outlaw Josey Wales in 1976 and the banker with crime syndicate connections, Boyle, oppositeWalter Matthau in 1973's Charley Varrick.
Vernon is probably best remembered for his role as the deadly serious Dean Vernon Wormer of mythical Faber College in 1978's enduring cult classic, Animal House (a role that he would reprise in the short-lived television sequel Delta House). Children will remember Vernon as the equally evil Mr. Prindle in the Disney film Herbie Goes Bananas and Sherman Krader in Ernest Goes to Camp.
Many of his later roles were also as villains, such as the warden's role in the women's prison picture Chained Heat. He played "Ted Jarrett" in The A-Team episode "Labor Pains" (1983). Vernon would make light of his villain image in the 1988 Blaxploitation spoof I'm Gonna Git You Sucka commenting that while he would seem to be "above playing an exploitation villain", many others (including Angie Dickinson, Jamie Lee Curtis, and Shelley Winters) have appeared in similar roles. In 1986, he played the Principal in the Disney Sunday Movie Fuzz Bucket. Vernon took on a minor role in 1988 in Killer Klowns from Outer Space as well. Vernon was one of the leads for the short-lived 1990s series Acapulco H.E.A.T.
Known for his distinctively deep and commanding voice, he also did extensive voice work with the animated film Heavy Metal and on animated series such as The Marvel Super Heroesshow in the 1960s, where he played Iron Man, the Sub-Mariner and Major Glenn Talbot of The Incredible Hulk, to Batman: The Animated Series, where he played Rupert Thorne, and asGeneral Thunderbolt Ross in UPN's The Incredible Hulk, Wildfire where he played a horse, as well as Doctor Strange in an episode of the Fox Network's Spider-Man animated series in the 1990s. His final work was providing the voice of Dean Toadblatt in the TV series The Grim Adventures of Billy and Mandy and the voice of Judge Tohrin in Delgo.