Willis once stated: "I'm a mimimalist. I see things in simple ways ... It's human nature to define complexity as better. Well, it's not." In 1969, Director Aram Avakian hired Willis to work on his film End of the Road. This was Willis' first movie.

Willis went on to work for some of the most acclaimed Directors of what is now seen as a golden age of American film-making. He captured America's urban paranoia in three films he shot with Alan J. Pakula: Klute (1971), The Parallax View (1974) and All The President's Men (1976). He collaborated with Hal Ashby on The Landlord (1970), James Bridges on The Paper Chase (1973), and Herbert Ross on Pennies From Heaven (1981); as well as shooting all three of Coppola's Godfather films and working with Woody Allen on a succession of films that included Annie Hall (1977) and Manhattan (1979).

Up to the making of The Godfather (1972), Willis mostly used Mitchell reflex cameras with Baltar or Cooke lenses. After that he used Panavision equipment, which he had first used on Klute. Willis went back to using Mitchells on The Godfather Part II (1974), in order to retain the visual coherence of the two films. Asked in 2004 about shooting films digitally, he was skeptical: "The organics aren’t the same," he said. "The interpretive levels suffer", adding: "Digital is another form of recording an image, but it won’t replace thinking."

In the seven-year period up to 1977, Willis was the Director of photography on six films that received among them 39 Academy Award nominations, winning 19 times, including three awards for Best Picture. The fact that Willis did not receive a single nomination was a subject of some controversy. His frequent absence from this period's nominees has been ascribed both to his unhidden "antipathy for Hollywood" and his work being ahead of its time. He was once quoted as saying of Hollywood, "I don't think it suffers from an overabundance of good taste". Willis was later nominated twice, once for his inventive recreation of 1920s photography in Woody Allen's Zelig, and then for The Godfather Part III (1990). In 2009, at the inaugural Governors Awards, the Academy chose Willis as the recipient of the Academy Honorary Award for his life's work.

Willis also worked on the Allen films Interiors (1978), Stardust Memories (1980), A Midsummer Night's Sex Comedy (1982), Zelig (1983), Broadway Danny Rose (1984), and The Purple Rose of Cairo (1985). Allen said that working with Willis had helped to improve his technical skills, saying of him: "He's an Artist. He's got a great sense of humor--he taught me a lot."

Willis directed one film of his own, Windows, in 1980. He admitted the film had been a mistake, and later said of directing that he didn't really like it. "I've had a good relationship with actors," he reflected, "but I can do what I do and back off. I don't want that much romancing. I don't want them to call me up at two in the morning saying, 'I don't know who I am'". His last film was The Devil's Own (1997), directed by Pakula. Of his decision to retire, Willis said: "I got tired of trying to get actors out of trailers, and standing in the rain".

At a seminar on film-making he gave in 2003, Willis said, "It's hard to believe, but a lot of Directors have no visual sense. They only have a storytelling sense. If a Director is smart, he'll give me the elbow room to paint". He added: "It's the judgment they're paying for." In a later interview he explained that when he started out in films he "did things in visual structure that nobody in the Business was doing, especially in Hollywood", explaining: "I wasn't trying to be different; I just did what I liked". When asked by the interviewer how he applied his style to different genres and to working with different Directors, Willis answered: "You're looking for a formula; there is none. The formula is me."

Director Francis Ford Coppola said of Willis, "He has a natural sense of structure and beauty, not unlike a Renaissance Artist," while Willis was praised for his capacity to use "painterliness" to define "not just the look but the very meaning and feel of a film". Speaking of contemporary film-making in 2004, Willis said:

Willis died of cancer on May 18, 2014, ten days before his 83rd birthday, in North Falmouth, Massachusetts. ASC President Richard Crudo said: "He was one of the giants who absolutely changed the way movies looked. Up until the time of The Godfather and The Godfather Part II, nothing previously shot looked that way. He changed the way films looked and the way people looked at films."