Pascal was born on March 25, 1958, in Los Angeles, California. Her father, Anthony H. Pascal, was an economic researcher at the RAND Corporation who wrote about African American social inequality and the cost of AIDS. Her mother, Barbara Pascal, was a librarian and owner of an art bookstore, Artworks. Her family is Jewish. Pascal attended Crossroads School in Santa Monica, then worked as a bookkeeper at Crossroads School while getting her international relations degree at UCLA.

Pascal joined Columbia Pictures in 1988, where she was responsible for the development of films including: Groundhog Day, Little Women, Awakenings, and A League of Their Own. She left Columbia in 1994 and served for two years as the President of Production for Turner Pictures while Scott Sassa was president of Turner Entertainment. During her time at Turner, Pascal hired Damon Lee as a development director.

Pascal rejoined Columbia in 1996 as the studio’s President after Turner Pictures merged with Warner Bros. In 1999, Pascal became Chair of Columbia Pictures.

Pascal married Bernard Weinraub, a former foreign correspondent for The New York Times and playwright, in 1997. They reside in Brentwood, Los Angeles, with their son.

In 2001, Pascal was honored with the Women in Film’s Crystal Award, which recognizes those whose work has helped to expand the role of women in the entertainment industry. Pascal has been included in The Hollywood Reporter’s annual Women in Entertainment Power 100 list and Forbes’ ranking of the World’s 100 Most Powerful Women. As of 2014, she was ranked as the 28th most powerful woman in the world by Forbes, up from 36th in 2013.

Pascal was named Co-Chairperson of Sony Pictures Entertainment in September 2006. She also served as Chairman of SPE’s Motion Picture Group from December 2003 to February 2015. Pascal and SPE’s Chairman and CEO Michael Lynton led all of SPE’s lines of business, including: motion picture production, acquisition and distribution; television production, acquisition and distribution; television networks; digital content creation and distribution; operation of studio facilities; and development of new entertainment products, services and technologies.

In 2013, Pascal was elected to the Board of Governors of the Academy of Motion Picture Arts and Sciences.

In August 2014, in the wake of the 2014 Israel–Gaza conflict, alongside more than 190 members of the Hollywood entertainment industry, she signed a petition condemning Hamas started by Creative Community for Peace, a pro-Israeli non-profit organization. The petition read in part, “Hamas cannot be allowed to rain rockets on Israeli cities, nor can it be allowed to hold its own people hostage. Hospitals are for healing, not for hiding weapons. Schools are for learning, not for launching missiles. Children are our hope, not our human shields.”

On December 9, 2014, a group called “Guardians of Peace” hacked into Sony’s computer system, which led to the theft of internal company documents. The fallout became a major international diplomatic incident in North Korea–United States relations. In subsequent news coverage Pascal and producer Scott Rudin were noted to have had an exchange in these documents about Pascal’s upcoming encounter with President Barack Obama. Pascal joked that the president, who was Black, would possibly enjoy Django Unchained and The Butler (films which deal with slavery in the United States and the pre-civil rights era) or the comedy Think Like a Man which features an ensemble cast of black comedians. Rudin responded, “Ride Along, I bet he likes Kevin Hart.”

Color of Change, a civil rights organization, launched a petition in December 2014 calling upon Sony to fire Pascal from her role, arguing, “Pascal’s comments are confirmation of the manipulative, exploitative relationship corporations like Sony have with Black folks.” They added, “We must hold Pascal accountable here; not just for her horrendous comments, but also for her role at the helm of a corporate agenda that views Black America as one big, lucrative joke.”

Pascal’s contract with Sony was scheduled to expire in March 2015. On February 5, 2015, Pascal announced she would step down in May 2015 Pascal stated during a Women in the World discussion on February 11, 2015, that she had been “fired” by Sony.

Civil rights leader Al Sharpton suggested the apology was not sufficient, compared her to Donald Sterling, and called for more diversity in Sony’s hiring pool. A New York Times columnist denounced the media’s focus on Pascal’s communications and many other emails released by the hack as “Giving Material Aid to Criminals”, saying “at least the hackers are doing it for a cause. The press is doing it for a nickel.” In the popular press, coverage of the story was extended with actress and producer Lisa Kudrow suggesting Pascal should have known better, adding, “Don’t write anything you don’t want broadcast”. At the Writers Guild of America Awards 2014 on January 7, 2015, Kudrow, who was the presenter, mentioned the Sony hack again, arguing that it was disturbing “because Scott Rudin and Amy Pascal thought that was witty banter.”

Pascal started her own production company, with a four-year contract for funding and distribution via Sony Pictures Entertainment. The company, called Pascal Pictures, hired Rachel O’Connor as production chief and Ian Dalrymple to open and run a New York branch. Pascal Pictures was expected to continue Amy Pascal’s “book-friendly” focus, and Dalrymple’s office was expected to facilitate this. She produced the Ghostbusters reboot film and the Marvel Studios-produced Spider-Man: Homecoming, in addition to theatre and television work. TriStar President Hannah Minghella obtained rights to Maestra by L. S. Hilton with the intent for Pascal to produce the film. Pascal Pictures made a winning bid for a memoir by Zoë Quinn about “Gamergate” called Crash Override: How to Save the Internet from Itself, which was sold to Touchstone/Simon & Schuster for publication in September 2016. Pascal and Elizabeth Cantillon optioned rights for a TriStar TV series based on books by Eve Babitz set in 1960s-1970s Los Angeles. For a sum in the “mid-six to seven figures”, Pascal made a deal for Michael Diliberti’s Athena, about a descendant of the goddess Athena who is recruited to a secret organization. Together with Sony, Pascal obtained rights for the TV crime drama Darktown, which she plans to executive produce with Jamie Foxx.

In 2016, Pascal launched her production company Pascal Pictures which produced their first film Ghostbusters.

In May 2019, it was announced that Pascal and her production company Pascal Pictures is leaving Sony and moving to Universal Pictures for a first-look deal after 30 years at Sony Pictures.

In a 2020 interview with Vulture, Thandie Newton accused Pascal of making racially insensitive and demeaning demands of her for the film remake of Charlie’s Angels, a film Newton ended up declining to star in due to Pascal’s alleged behavior. Pascal responded by stating she was “horrified” by the story and had no recollection of it.