After many unsuccessful attempts at publishing stories in the highly regarded literary magazine, The American Mercury, his short story "Altar Boy" was accepted conditionally by the magazine's editor, H.L. Mencken. The acceptance of "Altar Boy" by The American Mercury was accompanied by a reply from Mencken that read: "Dear Mr. Fante, What do you have against a typewriter? If you transcribe this manuscript in type I'll be glad to buy it. Sincerely yours, H.L. Mencken."
By far, his most popular novel is the semi-autobiographical Ask the Dust, the third book in what is now referred to as "The Saga of Arturo Bandini" or "The Bandini Quartet". Bandini served as his alter ego in a total of four novels: Wait Until Spring, Bandini (1938), The Road to Los Angeles (chronologically, this is the first novel Fante wrote but it was unpublished until 1985), Ask the Dust (1939), and finally Dreams from Bunker Hill (1982), which was dictated to his wife, Joyce, towards the end of his life. Fante's use of Bandini as his alter ego can be compared to Charles Bukowski's character, Henry Chinaski. Bukowski was heavily influenced by John Fante (see below).
Other novels include Full of Life (1952), The Brotherhood of the Grape (1977), and 1933 Was a Bad Year (1985; incomplete). Two novellas, 'My Dog Stupid' and 'The Orgy' were published in 1986 under the title West of Rome. His short story collection, Dago Red, was originally published in 1940, and then republished with a few additional stories in 1985 under the title The Wine of Youth.
Recurring themes in Fante's work are poverty, Catholicism, family life, Italian-American identity, sports, and the writing life. Ask the Dust has been referred to over the years as a monumental Southern California/Los Angeles novel by a host of reputable sources (e.g.: Carey McWilliams, Charles Bukowski, and The Los Angeles Times Book Review). More than sixty years after it was published, Ask the Dust appeared for several weeks on the New York Times' Bestseller's List. Fante's clear voice, vivid characters, shoot-from-the-hip style, and painful, emotional honesty blended with humor and scrupulous self-criticism lends his books to wide appreciation. Most of his novels and stories take place either in Colorado or California. Many of his novels and short stories also feature or focus on fictional incarnations of Fante's father, Nick Fante, as a cantankerous wine tippling, cigar stub-smoking bricklayer.
Fante's screenwriting credits include the comedy-drama Full of Life (1957), based on his novel of the same name, which starred Judy Holliday and Richard Conte, and was nominated for Best Written American Comedy at the 1957 WGA Awards. He also co-wrote Walk on the Wild Side (1962), which stars Jane Fonda in her first credited film role, based on the novel by Nelson Algren. His other screenplay credits include Dinky, Jeanne Eagels, My Man and I, The Reluctant Saint, Something for a Lonely Man and Six Loves. As Fante himself often admitted, most of what he wrote for the screen was simply hackwork intended to bring in a paycheck,.
In the late 1970s, at the suggestion of novelist and poet Charles Bukowski, Black Sparrow Press began to republish the (then out-of-print) works of Fante, creating a resurgence in his popularity. When Black Sparrow was reconfigured on its founder's retirement in 2002, publication of John Fante's works was taken over by HarperCollins under the Ecco imprint, but not before Black Sparrow Press could publish the last of Fante's uncollected stories in The Big Hunger (2000). Full of Life: The Biography of John Fante was published by Stephen Cooper also in 2000, followed by The Fante Reader in 2003. Also available are two collections of letters, Fante/Mencken: A Personal Correspondence (1989) and Selected Letters (1991).
His papers are held by the University of California at Los Angeles library.
He is known to be one of the first writers to portray the tough times faced by many writers in L.A. Robert Towne has called Ask The Dust the greatest novel ever written about Los Angeles.
His work and style has influenced similar authors such as Charles Bukowski, who stated in his introduction to Ask The Dust "Fante was my god". He was proclaimed by Time Out magazine as one of America's “criminally neglected writers."
In 1987, Fante was posthumously awarded the PEN USA President's Award.
On October 13, 2009, Los Angeles City Council member Jan Perry put forward a motion, seconded by Jose Huizar, that the intersection of Fifth Street and Grand Avenue be designated John Fante Square. The site is outside the Los Angeles Central Library frequented by the young Fante, and where Charles Bukowski discovered Ask The Dust. On April 8, 2010, the author's 101st birthday, the Fante Square sign will be unveiled in a noon ceremony attended by Fante's family, fans and city officials.
He is also referenced in the song "Album of the Year" by The Good Life.
Dominique Deruddere directed the movie version of Wait Until Spring, Bandini, which was released in 1989. In March 2006, Paramount Pictures released Ask the Dust, directed by Robert Towne and starring Colin Farrell, Salma Hayek, and Donald Sutherland. In December 2006, a 2001 documentary film about Fante, entitled A Sad Flower in the Sand (directed by Jan Louter) aired on the PBS series Independent Lens.On January 18, 2001 the play, "1933" by Randal Myler and Brockman Seawell, based on the novel1933 was a Bad Year, premiered at the Denver Center for the Performing arts.