Shelton began acting in her late teens, and appeared in several television movies and films throughout the 1990s, including the 1993 film, The Sandlot, playing the lifeguard, Wendy Peffercorn, and 1997's fantasy film Warriors of Virtue, playing Princess Elysia. Shelton has since appeared in many films aimed at a teenage audience, including 1999's Never Been Kissed and 2001's Valentine, Sugar & Spice and Bubble Boy. Most of her other roles in the 2000s were in lower-budget, independent films, with the exception of her supporting role in 2005's Sin City. Shelton was also originally cast in the role of Annabeth Schott on the television series, The West Wing, but the role was eventually played by Kristin Chenoweth.

Shelton had a prominent role as Dr. Dakota Block in the Robert Rodriguez/Quentin Tarantino-directed film Grindhouse, appearing in both of the film's segments as the same character. Examining bodies is what she likes to do in her spare time as well, yet she likes the live women the best, as admitted to People Magazine.

In October 2008, CBS's new series Eleventh Hour, based on the British TV series of the same name, premiered with Shelton appearing as FBI Special Agent Rachel Young of the executive protection detail. She is soon to be named the hottest detective on a television series by MTV and the viewers as the ratings sky rocket.

• A Perfect Getaway (2009) (post-production)
• Untitled (2009) (post-production) .... Madeleine
• Women in Trouble (2009) (completed) .... Cora
• Our Lady of Victory (2008) (completed) .... Sister Sunday
  
• "Eleventh Hour" .... Rachel Young (9 episodes, 2008)
       - Flesh (2008) TV episode .... Rachel Young
       - Titans (2008) TV episode .... Rachel Young
       - Surge (2008) TV episode .... Rachel Young
       - Frozen (2008) TV episode .... Rachel Young
       - Containment (2008) TV episode .... Rachel Young
        (4 more)
• W. (2008/I) .... Fran
  ... aka W. - Ein missverstandenes Leben (Germany: DVD title)
• Planet Terror (2007) .... Dakota
  ... aka Grindhouse Presents: Robert Rodriguez's Planet Terror (USA: DVD title)
  ... aka Robert Rodriguez's Planet Terror (USA: complete title)
• The Fifth Patient (2007) .... Helen
• Death Proof (2007) .... Dr. Dakota Block - McGraw
  ... aka Grindhouse Presents: Quentin Tarantino's Death Proof (USA: DVD title)
  ... aka Grindhouse: Death Proof (International: English title)
  ... aka Quentin Tarantino's Death Proof (USA: complete title)
  ... aka Quentin Tarantino's Thunder Bolt (USA: informal alternative title)
• Grindhouse (2007) .... Dr. Dakota Block (segments "Planet Terror" / "Death Proof")
• The Last Kiss (2006) .... Arianna
• Jesus, Mary and Joey (2006) .... Mary O'Callahan
  ... aka Welcome Back Miss Mary (USA: cable TV title)
• American Dreamz (2006) .... Jessica
  ... aka American Dreamz (Australia)
• "American Dad!" .... Betsy (1 episode, 2005)
       - Deacon Stan, Jesus Man (2005) TV episode (voice) .... Betsy
• Don't Come Knocking (2005) .... Starlet
• Sin City (2005) .... The Customer
  ... aka Frank Miller's Sin City (USA: complete title)