The initial media exposure led to her co-hosting the Canadian game show Video & Arcade Top 10 (1991–2006). While auditioning for television and film roles, she worked on theatre productions of Romeo and Juliet and Arsenic and Old Lace.
Her first television acting role was as "Second Girl" on The Hidden Room in 1993. Her first recurring role was in the TV series TekWar in 1994 where she portrayed the role of Cowgirl. Her first movie role was in Jungleground (1995). Doig got her first big break with a starring role in the movie No Alibi in 2000. She also landed the title role in Gene Roddenberry's sci-fi TV series Andromeda where, from 2000 to 2005, she portrayed the Andromeda Ascendant ship's computer in three personas — as the ship's powerful AI (artificial intelligence) on the ship's screen, as the AI's hologram, and as Rommie, the android avatar of the AI.
In 2002, she played the female lead role of “Dr. Rowan LaFontaine” in the horror film Jason X, the tenth installment of the Friday the 13th film series. In a recurring role as Dr. Carolyn Lam, Doig appeared in 11 episodes of the ninth and tenth seasons of Stargate SG-1 between 2005–2007. In 2010, Doig appeared in six episodes in the remake of V as the alien physician Dr. Leah Pearlman. In 2012, she began playing the role of Liber8 terrorist Sonya Valentine in the Canadian science fiction TV series Continuum.
Lexa Doig dated actor Michael Shanks after they met on the set of Andromeda, where the former starred and the latter guest-starred in the 2001 episode "Star Crossed." They married on August 2, 2003, and they worked together again in the 2003 episode "Day of Judgment, Day of Wrath" of the same TV series. The couple were castmates in the final two seasons of Stargate SG-1. They worked together in the action thriller Tactical Force (2011), in which Doig portrayed an LAPD SWAT officer and Shanks played the role of a Russian mob leader. They have two children, a son and a daughter, in addition to Shanks' child from a previous relationship.
In 2017, Doig appears in a recurring role in the fifth season of Arrow as Talia al Ghul, and portrays DeAnn Anderson, one of the main roles in The Arrangement
