For some of his own genre work, Chabon has forged an unusual horror/fantasy fiction persona under the name of August Van Zorn. More elaborately developed than a pseudonym, August Van Zorn is purported to be a pen name for one Albert Vetch (1899–1963). In Chabon's 1995 novel Wonder Boys, narrator Grady Tripp writes that he grew up in the same hotel as Vetch, who worked as an English professor at the (nonexistent) Coxley College and wrote hundreds of pulp stories that were "in the gothic mode, after the manner of Lovecraft ... but written in a dry, ironic, at times almost whimsical idiom." A horror-themed short story titled "In the Black Mill" was published in Playboy in June 1997 and reprinted in Chabon's 1999 story collection Werewolves in Their Youth, and was attributed to Van Zorn.

Michael Chabon (pronounced, in his words, "Shea as in Shea Stadium, Bon as in Bon Jovi", i.e., /ˈʃeɪbɒn/) was born in Washington, DC to Robert Chabon, a physician and Lawyer, and Sharon Chabon, a Lawyer. Chabon said he knew he wanted to be a Writer when, at the age of ten, he wrote his first short story for a class assignment. When the story received an A, Chabon recalls, "I thought to myself, 'That's it. That's what I want to do. I can do this.' And I never had any second thoughts or doubts." Referring to popular culture, he wrote of being raised "on a hearty diet of crap". His parents divorced when Chabon was 11, and he grew up in Pittsburgh, Pennsylvania, and Columbia, Maryland. Columbia, where Chabon lived nine months of the year with his mother, was "a progressive planned living community in which racial, economic, and religious diversity were actively fostered." He has written of his mother's marijuana use, recalling her "sometime around 1977 or so, sitting in the front seat of her friend Kathy's car, passing a little metal pipe back and forth before we went in to see a movie.". He grew up hearing Yiddish spoken by his mother's parents and siblings.

Chabon attended Carnegie Mellon University for a year before transferring to the University of Pittsburgh, where he studied under Chuck Kinder and received a Bachelor of Arts in 1984. He then went to graduate school at the University of California, Irvine, where he received a Master of Fine Arts in creative writing.

In 1987, Chabon married the poet Lollie Groth. According to Chabon, the popularity of The Mysteries of Pittsburgh had adverse effects; he later explained, "I was married at the time to someone else who was also a struggling Writer, and the success created a gross imbalance in our careers, which was problematic." He and Groth divorced in 1991.

There are also instances in which character Surnames reappear from story to story. Cleveland Arning, a character in Chabon's 1988 debut novel, The Mysteries of Pittsburgh, is described as having come from a wealthy family, one that might be expected to be able to endow a building. Near the end of Wonder Boys (1995), it is mentioned that, on the unnamed college campus at which Grady Tripp teaches, there is a building called Arning Hall "where the English faculty kept office hours." Similarly, in Chabon's 1989 short story "A Model World," a character named Levine discovers, or rather plagiarizes, a formula for "nephokinesis" (or cloud control) that wins him respect and prominence in the meteorological field. In The Amazing Adventures of Kavalier & Clay (2000), a passing reference is made to the "massive Levine School of Applied Meteorology," ostensibly a building owned by New York University.

Chabon has provided several subtle hints throughout his work that the stories he tells take place in a shared fictional universe. One recurring character, who is mentioned in three of Chabon's books but never actually appears, is Eli Drinkwater, a fictional catcher for the Pittsburgh Pirates who died abruptly after crashing his car on Mt. Nebo Road. The most detailed exposition of Drinkwater's life appears in Chabon's 1990 short story "Smoke," which is set at Drinkwater's funeral, and refers to him as "a scholarly catcher, a redoubtable batsman, and a kind, affectionate person." Drinkwater was again referred to (though not by name) in Chabon's 1995 novel Wonder Boys, in which narrator Grady Tripp explains that his sportswriter friend Happy Blackmore was hired "to ghost the autobiography of a catcher, a rising star who played for Pittsburgh and hit the sort of home runs that linger in the memory for years."

Although Chabon has described his attitude toward Hollywood as "pre-emptive cynicism," for years the author has nevertheless engaged in sustained, and often fruitless, efforts to bring both adapted and original projects to the screen. In 1994, Chabon pitched a screenplay entitled The Gentleman Host to Producer Scott Rudin, a romantic comedy "about old Jewish folks on a third-rate cruise ship out of Miami." Rudin bought the project and developed it with Chabon, but it was never filmed, partly due to the release of the similarly themed film Out to Sea in 1997. In the nineties, Chabon also pitched story ideas for both the X-Men and the Fantastic Four movies, but was rejected.

When he finally decided to abandon Fountain City, Chabon recalls staring at his blank computer for hours, before suddenly picturing "a 'straitlaced, troubled young man with a tendency toward melodrama' trying to end it all." He began writing, and within a couple of days, had written 50 pages of what would become his second novel, Wonder Boys. Chabon drew on his experiences with Fountain City for the character of Grady Tripp, a frustrated Novelist who has spent years working on an immense fourth novel. The author wrote Wonder Boys in a dizzy seven-month streak, without telling his agent or publisher he'd abandoned Fountain City. The book, published in 1995, was a commercial and critical success.

Telegraph Avenue, adapted from an idea for a TV series pilot that Chabon was asked to write in 1999, is a social novel set on the borders between Oakland and Berkeley in the summer of 2004 that sees a "large cast of characters grapple with infidelity, fatherhood, crooked politicians, racism, nostalgia and buried secrets." Chabon said upon publication in an interview with the San Francisco Chronicle that the novel concerns "the possibility and impossibility of creating shared community spaces that attempt to transcend the limits imposed on us by our backgrounds, heritage and history." Five years in gestation, Telegraph Avenue had a difficult birth, Chabon telling the Guardian newspaper, "I got two years into the novel and got completely stymied and felt like it was an utter flop.... I had to start all over again, keeping the characters but reinventing the story completely and leaving behind almost every element." After starting out with literary realism with his first two novels and moving into genre-fiction experiments from The Amazing Adventures of Kavalier and Clay onward, Chabon feels that Telegraph Avenue is a significant "unification" of his earlier and later styles, declaring in an interview, "I could do whatever I wanted to do in this book and it would be OK even if it verged on crime fiction, even if it verged on magic realism, even if it verged on martial arts fiction.... I was open to all of that and yet I didn't have to repudiate or steer away from the naturalistic story about two families living their everyday lives and coping with pregnancy and birth and adultery and Business failure and all the issues that might go into making a novel written in the genre of mainstream quote-unquote realistic fiction, that that was another genre for me now and I felt free to mix them all in a sense." The novel has been optioned by film Producer Scott Rudin (who previously optioned and produced Wonder Boys), and Cameron Crowe is adapting the novel into a screenplay, according to Chabon.

When Scott Rudin was adapting Wonder Boys for the screen, the author declined an offer to write the screenplay, saying he was too busy writing The Amazing Adventures of Kavalier and Clay. Directed by Curtis Hanson and starring Michael Douglas, Wonder Boys was released in 2000 to critical acclaim and financial failure. Having bought the film rights to The Amazing Adventures of Kavalier and Clay, Rudin then asked Chabon to work on that film's screenplay. Although Chabon spent 16 months in 2001 and 2002 working on the novel's film adaptation, the project has been mired in pre-production for years.

He married the Writer Ayelet Waldman in 1993. They currently live together in Berkeley, California with their four children, Sophie Waldman Chabon (born 1994), Ezekiel "Zeke" Napoleon Waldman Chabon (born 1997), Ida-Rose Waldman Chabon (born June 1, 2001), and Abraham Wolf Waldman Chabon (born March 31, 2003). Chabon has said that the "creative free-flow" he has with Waldman inspired the relationship between Sammy Clay and Rosa Saks toward the end of The Amazing Adventures of Kavalier & Clay, and in 2007, Entertainment Weekly declared the couple "a famous—and famously in love—writing pair, like Nick and Nora Charles with word processors and not so much booze."

Chabon's work, however, remains popular in Hollywood, with Rudin purchasing the film rights to The Yiddish Policemen's Union, then titled Hatzeplatz, in 2002, five years before the book would be published. The same year, Miramax bought the rights to Summerland and Tales of Mystery and Imagination (a planned collection of eight genre short stories that Chabon has not yet written), each of which was optioned for a sum in the mid-six figures. Chabon also wrote a draft for 2004's Spider-Man 2, about a third of which was used in the final film. Soon after Spider-Man 2 was released, Director Sam Raimi mentioned that he hoped to hire Chabon to work on the film's sequel, "if I can get him," but Chabon never worked on Spider-Man 3.

In October 2004, it was announced that Chabon was at work writing Disney's Snow and the Seven, a live-action martial arts retelling of Snow White and the Seven Dwarfs to be directed by master Hong Kong fight Choreographer and Director Yuen Wo Ping. In August 2006, Chabon said that he had been replaced on Snow, sarcastically explaining that the producers wanted to go in "more of a fun direction."

In 2005, Chabon argued against the idea that genre fiction and entertaining fiction should not appeal to "the real Writer," saying that the Common perception is that "Entertainment ... means Jun K.... [But] maybe the reason for the junkiness of so much of what pretends to entertain us is that we have accepted—indeed, we have helped to articulate—such a narrow, debased concept of entertainment.... I'd like to believe that, because I read for entertainment, and I write to entertain. Period."

Although Chabon was uninvolved with the project, Director Rawson Marshall Thurber shot a film adaptation of The Mysteries of Pittsburgh in fall 2006. The film, which stars Sienna Miller and Peter Sarsgaard, was released in April 2008. In February 2008, Scott Rudin reported that a film adaptation of The Yiddish Policemen's Union was in pre-production, to be written and directed by the Coen brothers.

On the other hand, in Slate in 2007, Ruth Franklin said, "Michael Chabon has spent considerable Energy trying to drag the decaying corpse of genre fiction out of the shallow grave where Writers of serious literature abandoned it."

Chabon was a vocal endorser of Barack Obama during his 2008 election campaign, and wrote an enthusiastic opinion piece on Obama for the New York Review of Books, titled "Obama & the Conquest of Denver", in October 2008. Subsequently, Chabon included a brief, fictionalized 'cameo' by Obama in his 2012 novel Telegraph Avenue.

In April 2009, Chabon confirmed he had been hired to do revisions to the script for Disney's John Carter. In 2014, Chabon was also involved in writing lyrics for Mark Ronson's album Uptown Special. In July 2015, Chabon was hired to do revisions to the script for Disney's Bob the Musical.

In late 2010, "An annotated, four-chapter fragment" from the unfinished 1,500 page manuscript Fountain City "complete with cautionary introduction and postscript" written by Chabon was included in McSweeney's 36.

In a 2012 interview with Guy Raz of Weekend All Things Considered, Chabon said that he writes from 10 p.m. to 3 a.m. each day, Sunday through Thursday. He tries to write 1,000 words a day. Commenting on the rigidity of his routine, Chabon said, "There have been plenty of self-destructive rebel-angel novelists over the years, but writing is about getting your work done and getting your work done every day. If you want to write novels, they take a long time, and they're big, and they have a lot of words in them.... The best environment, at least for me, is a very stable, structured kind of life."

In 2014, Amazon.com, a leading book distributor, was in a dispute with Hachette, a publisher. Hundreds of authors, Chabon included, condemned Amazon in an open letter because Amazon stopped taking pre-orders for books published by Hachette.

Since 2016, Chabon has been an outspoken critic of Donald Trump, both during his campaign for the presidency (signing a petition with over 400 other Writers against his presidency in May 2016), and during his administration. During an interview with The Guardian before Trump's inauguration in January 2017, Chabon remarked of the incoming President, "I really have no idea what to expect. He’s so unpredictable. He’s so mercurial. You know, I would be no more surprised if he stood up there and declared amnesty for all illegal immigrants to the United States than if he said he was going to take them all out to be shot. He’s like a random impulse generator." In a 2017 radio interview, Chabon spoke of President Trump and said: “Every morning I wake up and in the seconds before I turn my phone on to see what the latest news is, I have this boundless sense of optimism and hope that this is the day that he’s going to have a massive stroke, and, you know, be carted out of the White House on a gurney."

Chabon followed-up Moonglow in summer 2017 with the edited collection Kingdom of Olives and Ash: Writers Confront the Occupation, a non-fiction collection of essays by Writers concerning the continued Israeli occupation of the West Bank and Gaza, featuring contributions from Writers including Dave Eggers, Colum McCann, and Geraldine Brooks. Chabon co-edited the volume with Ayelet Waldman, and they both contributed essays to the collection. Chabon had previously weighed in on the Arab/Israeli conflict in 2010, having written an op-ed piece for the New York Times in June 2010 in which he noted the role of exceptionalism in Jewish identity, in relation to the "blockheadedness" of Israel's botching of the Gaza flotilla raid and the explanations that followed.