A native of Los Angeles, Smart began her career modelling in Italy and subsequently enrolled in acting school.

Her first role in film was in director Martin Kunert's anthology horror film Campfire Tales, followed by a minor part in Paul Verhoeven's Starship Troopers (1997). In 1998, Smart played a role in Dee Snider's Strangeland. She garnered widespread recognition after appearing in the mainstream teen drama Varsity Blues (1999), as well as for her recurring role as Ruby on the television series Felicity (1999–2001). She followed this with a lead role in the college sex comedy Road Trip (2000), and co-starred in Jerry Zucker's ensemble comedy Rat Race (2001). She had a lead role opposite Ashton Kutcher in the sci-fi drama The Butterfly Effect (2004).

Smart co-starred with Ryan Reynolds and Anna Faris in Just Friends (2005), followed by the sports drama Peaceful Warrior (2006). From 2011 to 2012, she had a recurring role as Jasmine Hollander on the series Shameless. She subsequently starred in Tyler Perry's comedy The Single Moms Club (2014). Since 2020, Smart has starred as Barbara Whitmore in the DC Universe/The CW superhero drama series Stargirl.