Smart's first film role was in director Martin Kunert's film Campfire Tales, followed by a small role as Queenie in the 1996 rendition of John Updike's short story, "A&P". She had a minor role in the 1997 film Starship Troopers as the co-pilot for (and friend of) Carmen Ibanez (Denise Richards). She had a starring role in the mini-series titled The 70s, playing a young woman from Ohio. In 1999, Smart played the girlfriend of a popular football player (played by James Van Der Beek) in the film Varsity Blues. Also, Smart appeared in the series Felicity, as a girlfriend of Scott Foley's character.

She subsequently appeared in a number of films catering to a teenage audience, many of which were successful, including Road Trip (2000) and The Butterfly Effect (2004). In 2002, she was ranked #27 in Stuff magazine's "100 Sexiest Women in the World" and in 2004, she was nominated for "Best Kiss" at the MTV Movie Awards for her role in Starsky & Hutch. She's been paired twice as a couple with Breckin Meyer in films Road Trip and Rat Race.

In 2005, Smart co-starred with Ryan Reynolds in the romantic comedy film Just Friends, which had a total domestic box office gross of $32,619,761 and a total worldwide box office of $50,817,598. Smart also had a small role in the American sitcom Scrubs, playing Jamie Moyer, one of main character J.D.'s love interests. On September 1, 2006, Crank was released, in which she plays the girlfriend of the lead character, Chev (played by Jason Statham).

Smart was a regular cast member in the short-lived 2006 CBS television series Smith. She also has voiced some of the characters in the animated series Robot Chicken, created by Seth Green. Smart appeared as Joy in the 2006 movie Peaceful Warrior, starring Scott Mechlowicz and Nick Nolte.

• Crank 2: High Voltage (2009) (completed) .... Eve
  
• Robot Chicken: Star Wars Episode II (2008) (TV) (voice) .... Princess Leia Organa
• Seventh Moon (2008) .... Melissa
• Mirrors (2008) .... Angela Carson
  ... aka Oglinzi malefice (Romania)
• Love N' Dancing (2008) .... Jessica Donovan
• Life in Flight (2008) .... Catherine
• The Meant to Be's (2008) (TV) .... Janine
• "Robot Chicken" .... Strawberry Shortcake / ... (4 episodes, 2005-2007)
       - Moesha Poppins (2007) TV episode (voice) .... Sailor Moon / Strawberry Shortcake
       - That Hurts Me (2005) TV episode (voice) .... Drew Barrymore/Various
       - Operation Rich in Spirit (2005) TV episode (voice) .... Strawberry Shortcake / Little Girl
       - Nightmare Generator (2005) TV episode (voice) .... Baker
• "Smith" .... Annie (7 episodes, 2006-2007)
       - Seven (2007) TV episode .... Annie
       - Six (2007) TV episode (credit only) .... Annie
       - Five (2007) TV episode .... Annie
       - Four (2007) TV episode .... Annie
       - Three (2006) TV episode .... Annie
        (2 more)
• Crank (2006) .... Eve
• Peaceful Warrior (2006) .... Joy
• Just Friends (2005) .... Jamie Palamino
  ... aka Just Friends - No Sex (Germany: DVD title)
  ... aka Simplement amis? (Canada: French title)
  ... aka Wild X-mas (Germany)
• The Best Man (2005) .... Sarah Marie Barker
  ... aka Best Man, Worst Friend (USA: TV title)
  ... aka Ein Trauzeuge zum Verlieben (Germany)
  ... aka Unhitched (USA: DVD title)
• Bigger Than the Sky (2005) .... Grace Hargrove/Roxanne
• Starsky & Hutch (2004) .... Holly
• Willowbee (2004) .... Burgler
• Win a Date with Tad Hamilton! (2004) .... Nurse Betty
• The Butterfly Effect (2004) .... Kayleigh
• Blind Horizon (2003) .... Liz Culpepper