Kosiński practiced the photographic arts, with one-man exhibitions to his credit in Warsaw's Crooked Circle Gallery (1957), and in the Andre Zarre Gallery in New York (1988). He watched surgeries, and read to terminally ill patients.

In 1962, Kosiński married an American steel heiress, Mary Hayward Weir. They divorced four years later. Weir died in 1968 from brain cancer, leaving Kosiński out of her will. He would fictionalize his marriage in his novel Blind Date, speaking of Weir under pseudonym Mary-Jane Kirkland. Kosiński later in 1968 married Katherina "Kiki" von Fraunhofer (1933 — 2007), a marketing consultant and a member of the Bavarian nobility.

The Painted Bird, Kosiński's controversial 1965 novel, is a fictional account that depicts the personal experiences of a boy of unknown religious and ethnic background who wanders around unidentified areas of Eastern Europe during World War II and takes refuge among a series of people, many of whom are brutally cruel and abusive, either to him or to others.

Steps (1968), a novel comprising scores of loosely connected vignettes, won the U.S. National Book Award for Fiction.

Kosiński was friends with Roman Polanski, with whom he attended the National Film School in Łódź, and said he narrowly missed being at Polanski and Sharon Tate's house on the night Tate was murdered by Charles Manson's followers in 1969, due to lost luggage. His novel Blind Date portrayed the Manson murders.

One of Kosiński's most significant works is Being There (1970), a satirical view of the absurd reality of America's media culture. It is the story of Chance the gardener, a man with few distinctive qualities who emerges from nowhere and suddenly becomes the heir to the throne of a Wall Street tycoon and a presidential policy adviser. His simple and straightforward responses to popular concerns are praised as visionary despite the fact that no one actually understands what he is really saying. Many questions surround his mysterious origins, and filling in the blanks in his background proves impossible.

Kosiński appeared 12 times on The Tonight Show Starring Johnny Carson during 1971–73, and The Dick Cavett Show in 1974, was a guest on the talk radio show of Long John Nebel, posed half-naked for a cover photograph by Annie Leibovitz for The New York Times Magazine in 1982, and presented the Oscar for screenwriting in 1982.

American Novelist David Foster Wallace described Steps as a "collection of unbelievably creepy little allegorical tableaux done in a terse elegant voice that's like nothing else anywhere ever". Wallace continued in praise: "Only Kafka's fragments get anywhere close to where Kosiński goes in this book, which is better than everything else he ever did combined." Samuel Coale, in a 1974 discussion of Kosiński's fiction, wrote that "the narrator of Steps for instance, seems to be nothing more than a disembodied voice howling in some surrealistic wilderness."

Kosiński himself addressed these claims in the introduction to the 1976 reissue of The Painted Bird, saying that "Well-intentioned Writers, critics, and readers sought facts to back up their claims that the novel was autobiographical. They wanted to cast me in the role of spokesman for my generation, especially for those who had survived the war; but for me survival was an individual action that earned the survivor the right to speak only for himself. Facts about my life and my origins, I felt, should not be used to test the book's authenticity, any more than they should be used to encourage readers to read The Painted Bird. Furthermore, I felt then, as I do now, that fiction and autobiography are very different modes."

The novel was made into a 1979 movie directed by Hal Ashby, and starring Peter Sellers, who was nominated for an Academy Award for the role, and Melvyn Douglas, who won the award for Best Supporting Actor. The screenplay was co-authored by award-winning Screenwriter Robert C. Jones with Kosiński. The film won the 1981 British Academy of Film and Television Arts (Film) Best Screenplay Award, as well as the 1980 Writers Guild of America Award (Screen) for Best Comedy Adapted from Another Medium. It was also nominated for the 1980 Golden Globe Best Screenplay Award (Motion Picture).

Kosiński wrote his novel Pinball (1982) for his friend George Harrison, having conceived of the idea for the book at least ten years before writing it.

In 1984, Polanski denied Kosiński's story in his autobiography. Journalist John Taylor of New York Magazine believes Polanski was mistaken. "Although it was a single sentence in a 461-page book, reviewers focused on it. But the accusation was untrue: Jerzy and Kiki had been invited to stay with Tate the night of the Manson murders, and they missed being killed as well only because they stopped in New York en route from Paris because their luggage had been misdirected." The reason why Taylor believes this is that "a friend of Kosiński's wrote a letter to the Times, which was published in the Book Review, describing the detailed plans he and Jerzy had made to meet that weekend at Polanski's house on Cielo Drive. Few people saw the letter." The NYM article does not contain the name of this friend, nor the particular issue of the Book Review in which this letter is supposed to have been published, nor names of the 'few' who may have read the letter.

Kosiński himself responded that he had never maintained that the book was autobiographical, even though years earlier he confided to Houghton Mifflin Editor Santillana that his manuscript "draws upon a childhood spent, by the Casual chances of war, in the remotest villages of Eastern Europe." In 1988, he wrote The Hermit of 69th Street, in which he sought to demonstrate the absurdity of investigating prior work by inserting footnotes for practically every term in the book. "Ironically," wrote theatre critic Lucy Komisar, "possibly his only true book ... about a successful author who is shown to be a fraud."

Kosiński's novels have appeared on The New York Times Best Seller list, and have been translated into over 30 languages, with total sales estimated at 70 million in 1991.

According to Eliot Weinberger, an American Writer, Essayist, Editor and translator, Kosiński was not the author of The Painted Bird. Weinberger alleged in his 2000 book Karmic Traces that Kosiński was not fluent in English at the time of its writing.

Terence Blacker, a profitable English publisher (who helped publish Kosiński's books) and author of children's books and mysteries for adults, wrote an article published in The Independent in 2002:

He also played the role of Bolshevik revolutionary and Politburo member Grigory Zinoviev in Warren Beatty's film Reds. The Time magazine critic wrote: "As Reed's Soviet nemesis, Novelist Jerzy Kosinski acquits himself nicely–a tundra of ice against Reed's all-American fire." Newsweek complimented Kosinski's "delightfully abrasive" performance.

The article found a more realistic picture of Kosiński's life during the Holocaust — a view which was supported by biographers Joanna Siedlecka and Sloan. The article asserted that The Painted Bird, assumed to be semi-autobiographical, was largely a work of fiction. The information showed that rather than wandering the Polish countryside, as his fictional character did, Kosiński spent the war years in hiding with Polish Catholics.