Eszterhas went on to be a senior Editor from 1971 to 1975 for Rolling Stone. He became a National Book Award nominee for his nonfiction work Charlie Simpson's Apocalypse in 1974.

In 1974, Eszterhas married Gerri Javor. They had two children together and divorced in 1994. That same year, Eszterhas married Naomi Bakar, and they had four children. In 1990, Eszterhas learned that his father was then being investigated by the U.S. Department of Justice for writing anti-Semitic propaganda in Hungary during the 1930s and early 1940s. He refused further contact with his father after this revelation, which he later claimed to have regretted, saying "When [my father] was in a Hungarian old-age home, the Nurses kept calling and saying, 'He’s dying, and he needs to see you.' Not going was a huge mistake. I’ve asked God to forgive me, but I don’t think I’ll be forgiven.". Eszterhas is a Republican .

Eszterhas' first produced screenplay was F.I.S.T., directed by Norman Jewison. Eszterhas contributed to the script of 1983's highly successful Flashdance, and wrote the screenplays for Jagged Edge, Jade, Betrayed, Sliver, and Basic Instinct.

In 1989, Eszterhas planned to leave Creative Artists Agency because an old friend was restarting his agency. Michael Ovitz, then the chairman of CAA, threatened to prevent CAA actors from acting in Eszterhas' Future projects. Eszterhas wrote a letter that loosened the stranglehold that CAA had on Hollywood.

In 1995, Eszterhas wrote Showgirls, which won that year's Golden Raspberry Award for "Worst Screenplay". Despite the negative press, the film enjoyed cult success on the home video market, generating more than $100 million from video rentals and became one of MGM's top twenty all-time bestsellers.

The failure of Burn Hollywood Burn took a toll on Eszterhas' career: none of the screenplays he wrote between 1997 and 2006 were produced. However, Children of Glory, a Hungarian language film based upon his screenplay, was released in 2006. The film focuses upon both the 1956 Hungarian Revolution and the Blood in the Water match at the 1956 Melbourne Olympics. Children of Glory was entered by invitation in the official section of 2007 Berlin Film Festival.

Eszterhas has written several best-selling books, including Hollywood Animal, an autobiography about politics in Hollywood, which superimposes his life as a young immigrant in the United States on his life as a powerful Hollywood player. A third book, The Devil's Guide to Hollywood, was published in September 2006.

His book Crossbearer: A Memoir of Faith was published in 2008. It tells the story of his return to the Roman Catholic Church and his new-found devotion to God and family after surviving a throat cancer diagnosis in 2001. Eszterhas admitted smoking four packs of Salem Light cigarettes a day, as well as drinking heavily. He underwent surgery to remove 80% of his larynx, and had a trachea fitted.

In 2011, it was announced that actor-director Mel Gibson had commissioned a screenplay from Eszterhas: a historical biopic on Judah and The Maccabees, titled M.C.K.B.I. The film was to be distributed by Warner Bros. The announcement generated controversy. In a 2008 interview, Eszterhas had written that "Mel shared the mind-set of Adolf Hitler." In a February 2012 interview with Andrew Goldman of The New York Times, Goldman said to Eszterhas: "[Gibson's] film The Passion of the Christ was widely considered anti-Semitic. Then, during a 2006 arrest for drunken driving, he ranted that 'the Jews are responsible for all the wars in the world.' Is he the right Director?" Eszterhas' reply was: "... Adam Fogelson, Universal Pictures' chairman, said to [Gibson], 'Why do you want to do this story?" Mel said, 'Because I think I should.' I liked that answer very much." When asked about their shared Catholic faith, Eszterhas said of Gibson, "In my mind, his Catholicism is a figment of his imagination." By April 2012, Warner Bros. had cancelled the project; the film's last draft was dated February 20, 2012. Eszterhas claimed that the break was caused by Gibson's violent outbursts and anti-Semitism, while Gibson blamed a bad script. Eszterhas later wrote a book Heaven and Mel about his experiences working with Gibson.