Sokoloff was born in San Francisco, California to Jewish American parents Howard Sokoloff (a doctor) and Cindi Sussman (a former caterer). She began acting at the age of 12 when she was cast as Gia Mahan in the sitcom Full House. Her breakthrough role came in 1998 when she was cast in the drama The Practice as Lucy Hatcher. She also had a two-episode stint as a nanny in Desperate Housewives, which included a now famous nude scene.

Aside from television, Sokoloff has also starred in many movies, including Whatever It Takes, The Tollbooth, Dude, Where's My Car?, and Sugar & Spice.

When not working, Sokoloff enjoys music and has a large guitar collection, along with a band named Smittin, in which she sings and plays rhythm guitar. On February 17, 2006, she released her first CD, called GRATEFUL.

Sokoloff has dated actors James Franco and Shane West.