Esposito, an Italian-American, was born in Brooklyn, New York, the daughter of Phyllis, an interior decorator, and Robert Esposito, a computer consultant and music producer. She has one older sister. Esposito grew up and attended St.Teresa School in Staten Island, and graduated from Moore Catholic High School in Staten Island.[citation needed]

Esposito made her first television appearance in Law & Order in 1996, but she is best known as Stacey in the prime time hit Spin City. She also appeared in I Still Know What You Did Last Summer playing Nancy, who is killed when a spear impales her chest. One of her more notable roles was as Ruby in Spike Lee's Summer of Sam in 1999, which was set against the mid-1970s backdrop of the Son of Sam murders. She originally had the Mira Sorvino role in Summer of Sam, but had to take a different role due to scheduling conflicts. Esposito's next film was Wes Craven Presents: Dracula 2000.

In 2000, Esposito appeared on Law & Order: SVU as a sexually assaulted TV reporter. She played Don Cheadle's girlfriend, Ria, in the Academy Award-winning film Crash. Esposito was part of the cast for the now cancelled WB show Related in which she played Ginnie Sorelli. She also played a Lieutenant in the NYPD in the 2004 film Taxi. She recently played a love interest to Denis Leary's character in the FX dramedy Rescue Me. Most recently, Esposito appeared on television as Andrea Belladonna in the ABC comedy, Samantha Who?. She also appeared in the NBC medical drama "Mercy".

Esposito will appear in the 2011 film Killer in the Family, alongside Holly Marie Combs and James Denton.

Esposito dated Benjamin Bratt for eight months between 1996 and 1997. She later married Bradley Cooper on December 30, 2006. However, in April 2007, she filed for divorce. On August 24, 2007 court papers were filed that set a final date of November 10 for the official termination of the couple's marriage.

Esposito is now engaged to tennis player Mark Philippoussis.