He began writing as a child and wrote constantly. He attended high school at Harbord Collegiate Institute and North Toronto Collegiate Institute. A keen interest in science, especially botany and lepidopterology, led him to enter the Honours Science program at the University of Toronto in 1963, but he switched to Honours English Language and Literature later in his first year.

Cronenberg’s fascination with the film Winter Kept Us Warm (1966), by classmate David Secter, sparked his interest in film. He began frequenting film camera rental houses, learning the art of filmmaking, and made two 16mm films (Transfer and From the Drain). Inspired by the New York underground film scene, he founded the Toronto Film Co-op with Iain Ewing and Ivan Reitman. After taking a year off to travel in Europe, he returned to Canada in 1967 and graduated from University College of the University of Toronto at the top of his class.

Cronenberg lives in Toronto. He married his first wife, Margaret Hindson, in 1972: their seven-year marriage ended in 1979 amidst personal and professional differences. They had one daughter, Cassandra Cronenberg. His second wife was film editor Carolyn Zeifman, to whom he was married until her death in 2017. The couple met on the set of Rabid while she was working as a production assistant. They have two children, Caitlin and Brandon. In the book Cronenberg on Cronenberg (1992), he revealed that The Brood was inspired by events that occurred during the unraveling of his first marriage, which caused both Cronenberg and his daughter Cassandra a great deal of turmoil. The character Nola Carveth, mother of the brood, is based on Cassandra’s mother. Cronenberg said that he found the shooting of the climactic scene, in which Nola was strangled by her husband, to be “very satisfying”.

Aside from The Dead Zone (1983) and The Fly (1986), Cronenberg has not generally worked within the world of big-budget, mainstream Hollywood filmmaking, although he has had occasional near misses. At one stage he was considered by George Lucas as a possible director for Return of the Jedi (1983) but was passed over. Cronenberg also worked for nearly a year on a version of Total Recall (1990), but experienced “creative differences” with producers Dino De Laurentiis and Ronald Shusett; a different version of the film was eventually made by Paul Verhoeven. A fan of Philip K. Dick’s, author of “We Can Remember it For You Wholesale”, the short story upon which the film was based, Cronenberg related in the 1992 biography/overview of his work, Cronenberg on Cronenberg, that his dissatisfaction with what he envisioned the film to be and what it ended up being pained him so greatly that for a time, he suffered a migraine just thinking about it, akin to a needle piercing his eye.

Cronenberg received the Special Jury Prize at the 1996 Cannes Film Festival for Crash. In 1999, he was inducted onto Canada’s Walk of Fame, awarded the Silver Bear Award at the 49th Berlin International Film Festival. and that November received the Governor General’s Performing Arts Award, Canada’s highest honour in the performing arts.

In 2002, he was made an Officer of the Order of Canada, and was promoted to Companion of the Order of Canada (the order’s highest rank) in 2014. In 2006 he was awarded the Cannes Film Festival’s lifetime achievement award, the Carrosse d’Or. In 2009 Cronenberg received the Légion d’honneur from the government of France. The following year Cronenberg was named an honorary patron of the University Philosophical Society, Trinity College, Dublin. In 2012, he received the Queen Elizabeth II Diamond Jubilee Medal.

Cronenberg has appeared on various “Greatest Director” lists. In 2004, Science Fiction magazine Strange Horizons named him the second greatest director in the history of the genre, ahead of better known directors such as Steven Spielberg, James Cameron, Jean-Luc Godard, and Ridley Scott. In the same year, The Guardian listed him 9th on their list of “The world’s 40 best directors”. In 2007, Total Film named him as the 17th greatest director of all-time. Film professor Charles Derry, in his overview of the horror genre Dark Dreams, called the director one of the most important in his field, and that “no discussion of contemporary horror film can conclude without reference to the films of David Cronenberg.”

Cronenberg has said that his films should be seen “from the point of view of the disease”, and that in Shivers, for example, he identifies with the characters after they become infected with the anarchic parasites. Disease and disaster, in Cronenberg’s work, are less problems to be overcome than agents of personal transformation. Of his characters’ transformations, Cronenberg said, “But because of our necessity to impose our own structure of perception on things we look on ourselves as being relatively stable. But, in fact, when I look at a person I see this maelstrom of organic, chemical and electron chaos; volatility and instability, shimmering; and the ability to change and transform and transmute.” Similarly, in Crash (1996), people who have been injured in car crashes attempt to view their ordeal as “a fertilizing rather than a destructive event”. In 2005, Cronenberg publicly disagreed with Paul Haggis’ choice of the same name for the latter’s Oscar-winning film Crash (2004), arguing that it was “very disrespectful” to the “important and seminal” J.G. Ballard novel on which Cronenberg’s film was based.

In Cronenberg on Cronenberg, the director further elaborated that he was raised in a secular Jewish home, and while he and his family had no disdain towards any religion, such matters were not discussed. In the same book, Cronenberg said that in his teens he went through a phase where he wondered about the existence of God, but ultimately came to the conclusion that the God concept was developed to cope with the fear of death. In a 2007 interview, Cronenberg explained the role atheism plays in his work. He stated, “I’m interested in saying, ‘Let us discuss the existential question. We are all going to die, that is the end of all consciousness. There is no afterlife. There is no God. Now what do we do.’ That’s the point where it starts getting interesting to me.”

Cronenberg has collaborated with composer Howard Shore on all of his films since The Brood (1979), (see List of noted film director and composer collaborations) with the exception of The Dead Zone (1983), which was scored by Michael Kamen. Other regular collaborators include actor Robert Silverman, art director Carol Spier, sound editor Bryan Day, film editor Ronald Sanders, his sister, costume designer Denise Cronenberg, and, from 1979 until 1988, cinematographer Mark Irwin. In 2008, Cronenberg directed Howard Shore’s first opera, The Fly.

In 2008, Cronenberg realized two extra-cinematographic projects: the exhibition Chromosomes at the Rome Film Fest, and the opera The Fly at the LaOpera in Los Angeles and Theatre Châtelet in Paris. In July 2010, Cronenberg completed production on A Dangerous Method (2011), an adaptation of Christopher Hampton’s play The Talking Cure, starring Keira Knightley, Michael Fassbender, and frequent collaborator Viggo Mortensen. The film was produced by independent British producer Jeremy Thomas.

In 2012, his film Cosmopolis competed for the Palme d’Or at the 2012 Cannes Film Festival.

For a time it appeared that, as Eastern Promises producer Paul Webster told Screen International, a sequel is in the works that would reunite the key team of Cronenberg, Steven Knight, and Viggo Mortensen. The film was to be made by Webster’s new production company Shoebox Films in collaboration with Focus Features, and shot in early 2013. However, in 2012, Cronenberg commented that the Eastern Promises sequel had fallen through due to budget disagreement with Focus Features.

Filming for Cronenberg’s next film, a satire drama entitled Maps to the Stars (2014)—with Julianne Moore, Mia Wasikowska, John Cusack, and Robert Pattinson—began on July 8, 2013 in Toronto, Ontario and Los Angeles. This was the first time Cronenberg filmed in the United States.

The opening of the “David Cronenberg: Evolution” Toronto International Film Festival (TIFF) exhibition occurred on October 30, 2013. Held at the TIFF Bell Lightbox venue, the exhibition paid tribute to the director’s entire filmmaking career and the festival’s promotional material referred to Cronenberg as “one of Canada’s most prolific and iconic filmmakers”. The exhibition was shown internationally following the conclusion of the TIFF showing on January 19, 2014.

On June 26, 2014, Cronenberg’s short film The Nest was published on YouTube. The film was commissioned for “David Cronenberg – The Exhibition” at EYE Film Institute in Amsterdam and was available on YouTube for the duration of the exhibition, until September 14, 2014. Also in 2014, Cronenberg published his first novel, Consumed.

In 2014, he was made a Member of the Order of Ontario in recognition for being “Canada’s most celebrated internationally acclaimed filmmaker”.

In April 2018, it was announced that Cronenberg would receive the honorary Golden Lion at the 75th Venice International Film Festival.