He graduated from The Fieldston School in 1963 and from Harvard College, magna cum laude, in 1966. While attending Harvard College, Toback took what he claims to be the largest single dose of LSD in history. He remained under the influence of the drug for eight days before being administered an “antidote” by neuropsychiatrist Max Rinkel. According to Toback, he lost all fear of death due to this experience.

In 1974, Toback’s screenplay The Gambler was produced. Much of the film was shot at City College. His directorial début was the 1978 film Fingers, remade 28 years later by Jacques Audiard as The Beat That My Heart Skipped. Toback followed Fingers with Love and Money in 1982. Toback wrote and directed Exposed in 1983; The Pick-up Artist in 1987; and the documentary The Big Bang in 1989. Toback wrote the original screenplay for Bugsy, which won the Golden Globe for Best Picture and was nominated for ten Academy Awards including Best Original Screenplay. Toback won the Los Angeles Film Critics’ Award for Best Original Screenplay and a similar award from the readers of Premiere Magazine.

An article in a 1989 issue of Spy magazine detailed how Toback would “hang out on the streets of the Upper West Side in New York City, and approach women. According to the story, he would in rapid-fire fashion tell them that he was a Hollywood director and offer to show them his Directors Guild of America card. The pitch invariably ended up with an invite to meet privately—sometimes at an outlandishly late hour—to talk about appearing in one of his films”.

In 1997, Toback wrote and directed the comedy Two Girls and a Guy, and in 1999, he wrote and directed Black and White in collaboration with members of Wu-Tang Clan. He then wrote and directed Harvard Man starring Adrian Grenier in 2001. In 2004, Toback wrote and directed When Will I Be Loved and in 2008, Toback directed Tyson, a documentary about boxer Mike Tyson.

In 2008 and 2015 Gawker articles described Toback as a “pick-up artist”.

Toback teamed with Alec Baldwin in 2013 to create and release a full-length movie called Seduced and Abandoned, which features a look into how movies are financed. Toback referred to the documentary style film as a cinematic romp. The HBO film shows Toback and Baldwin at the 2012 Cannes Film Festival searching for funding for a movie.

On October 22, 2017, the Los Angeles Times reported that 38 women have accused Toback of sexual harassment or assault. Toback denied these allegations, saying he had not met the women, or that if he had, it “was for five minutes” about which he had “no recollection”. The alleged harassment occurred at meetings framed as interviews or casting auditions in places such as hotel rooms, movie trailers, or a public park where Toback asked questions pertaining to the women’s sex lives and rubbed his crotch on them or masturbated. Accusers include actresses Rachel McAdams, Selma Blair, Terri Conn,, Natasha Leggero,, Caterina Scorsone, Julianne Moore, Becky Wahlstrom, and musician Louise Post. Toback claimed he was taking medication at the time of the alleged assaults that made it “biologically impossible” for the alleged actions to occur.

In January 2018, Los Angeles Times journalist Glenn Whipp reported that since the Times published its article in October 2017, 395 women contacted the newspaper and said that Toback had sexually harassed them. The accounts stretch over a 40-year period. Toback has denied all these allegations as well. As of January 2018 Toback has been accused by at least 38 women.

In April 2018, Los Angeles County prosecutors declared they would not be pressing any charges against Toback. In one case the alleged victim did not turn up for an interview, and the rest were beyond the statute of limitations. Two of the declined cases involved misdemeanors, three involved felonies.