Kristanna started her acting career in 1994, playing "Danielle 'Dani' Andropoulos #3" on an episode of As The World Turns, and she appeared in several television shows and films, including regular appearances on the television shows Philly, Unhappily Ever After, and Boy Meets World. In 1998 she starred in Mortal Kombat: Conquest as "Taja". She is probably best known for her performance as the cyborg T-X (Terminatrix) in the 2003 movie Terminator 3: Rise of the Machines. In 2004, she appeared in a German television movie, Die Nibelungen (also known as "Dark Kingdom: The Dragon King" or "Sword of Xanten"), which aired as a 2-part mini-series and set a ratings record. Subsequently, she starred as the leading character in the 2006 film version of the video game BloodRayne, and appeared in director Uwe Boll's film version of the video game Dungeon Siege, called In the Name of the King.
She appeared in 10 episodes of the fourth season of The L Word, which debuted in January 2007. Additionally, she starred as the title character in the Sci-Fi Channel's series Painkiller Jane which aired from April to September 2007.