Mack was born in Preetz, Schleswig-Holstein, Germany to American parents, Mindy and Jonathan Mack. Her father was an opera singer performing there. The Mack family moved back to the United States when she was two years old. She has an older brother, Shannon, and a younger sister, Robyn.
She began her acting career at the age of four in commercials for "German Chocolate". Mack then went into modeling for a short period because her mother thought she "looked cute in clothes". She began studying at The Young Actors Space in Los Angeles when she was seven. Her first major TV role came in an episode of the WB series 7th Heaven, in which she gained a lot of attention playing a teenager who cut herself. In 2000, she starred in the short-lived series Opposite Sex. She also starred beside her former Smallville castmate Sam Jones III in an R. L. Stine miniseries The Nightmare Room. Her filmography includes Eric Stoltz's directorial debut My Horrible Year!, in which she plays a girl having great difficulties in her life as she turns 16, and Camp Nowhere. Mack starred as Chloe Sullivan, one of Clark Kent's best friends, in the CW hit series Smallville. In the summer of 2006, Mack's voice was heard as the sister of the main character in the Warner Bros. CGI movie The Ant Bully. That year she also provided the voice of a museum curator named Clea in an episode of The Batman. In November 2008, Mack began directing for the first time, taking the reins on the Smallville episode "Power", which aired January 29, 2009. Since May 2009, Mack has been part of a project with the Iris Theatre Company which performed a piece of experimental theater at the Prague Fringe Festival. She voiced Power Girl in the Warner Premiere animated feature, Superman/Batman: Public Enemies, released on September 29, 2009. In May 2010 it was announced that Mack will not be appearing as a series regular on the final season of Smallville, but will return for several episodes. At the 2010 San Diego Comic Con it was mentioned that Allison Mack may still be considered a series regular, as she would appear in several episodes. Mack returned for five episodes in the tenth season, being billed as a series regular for the episodes she appeared in. She also eventually appeared in the two-part series finale. It was announced in March 2012 that Allison was cast in Season 2 of the TV Series Wilfred in a recurring role. She will play a love interest for the lead character Ryan, played by Elijah Wood.