Louis-Dreyfus was born in New York City. Her American-born mother, Judith (nee LeFever), was a writer and special needs tutor, and her French-born father, Gerard Louis-Dreyfus, chaired Louis Dreyfus Energy Services. She is a great-great-granddaughter of Leopold Louis-Dreyfus, who in 1851 founded the Louis Dreyfus Group, a French commodities and shipping conglomerate, which members of her family control into the 21st century. Her paternal grandfather, Pierre Louis-Dreyfus, was president of the Louis Dreyfus Group.

In the early 1990s, Louis-Dreyfus became famous for the role of Elaine Benes on NBC's Seinfeld. She played the role for nine seasons, appearing in all but three episodes. One of the episodes that she did not appear in was the inaugural pilot episode, "The Seinfeld Chronicles", because her character was not initially intended to be a part of the series. It was only after the first episode that NBC executives felt the show was too male-centric, and demanded that creators Jerry Seinfeld and Larry David add a woman to the cast. It was revealed in the commentary on the DVD package that the addition of a female character was the condition for commissioning the show. Louis-Dreyfus won the role over several other actresses who would also eventually enjoy their own TV success, including Patricia Heaton, Rosie O'Donnell and Megan Mullally.  On the "Notes About Nothing" featurette on the DVD package, Seinfeld says that Louis-Dreyfus' ability to eat a peanut M&M without breaking the peanut aptly describes the actress: "She cracks you up without breaking your nuts."  Her performance on the series was met with critical acclaim, and she was a regular winner and nominee at television award shows throughout the 1990s. Her performance earned her two Golden Globe Award nominations, winning once in 1994, nine Screen Actors Guild Award nominations, winning one in 1995 and two in both 1997 and 1998, and seven American Comedy Awards, winning five times in 1993, 1994, 1995, 1997 and 1998. In 1996, she received the Primetime Emmy Award for Outstanding Supporting Actress in a Comedy Series, an award she was nominated for on seven occasions from 1992 to 1998. After receiving the award, Louis-Dreyfus claimed the win was a "shocker", and that after being in both positions, it was "much better to win than to lose."  In 1998, Seinfeld decided to end the series after nine seasons. The series finale aired on May 14 and was one of the most watched TV events in history, with over 76 million people tuning in.  During her time on Seinfeld she appeared in several films, including Fathers' Day, opposite Robin Williams and Billy Crystal, and Woody Allen's Oscar-nominated Deconstructing Harry.

Did she ever win an Emmy for the role?
Her performance on the series was met with critical acclaim, and she was a regular winner and nominee at television award shows throughout the 1990s.