Jeremy Sisto was born in Northern California in a small town called Grass Valley. His film debut was in the movie Grand Canyon (1991). He studied at UCLA for a while and then started acting full time. Jeremy likes to play Bocce (Italian Bowling) and play his guitar in his spare time.

Sisto played a killer in Hideaway, a rich brat in Clueless and White Squall, Jesus in the eponymous mini-series, a patient diagnosed with multiple personality disorder in the short film Inside, a former drug addict in Thirteen, and an abusive husband in Waitress. Sisto also played the character Billy in the HBO series Six Feet Under. He also appeared in the 2003 of the WB's Dawson's Creek.

Besides acting, Sisto has worked behind the scenes. In 1998, he produced the unreleased movie Taken, together with his friend Ethan Embry. He also produced the films Three Women of Pain and Paranoia 1.0. In April 2003, he started his own production company, Dima Entertainment. In 2006, he appeared on Broadway in Festen. In the same year, he starred in the short-lived NBC drama series Kidnapped.

In 2008, Sisto joined the cast of the crime drama Law & Order as Detective Cyrus Lupo, replacing the outgoing Milena Govich. He had previously appeared on the show as a lawyer in the previous season's finale.

Sisto is currently starring in the American television comedy series Suburgatory which premiered on ABC in the fall of 2011.