Vandervoort was born and raised in Toronto, Ontario, Canada. She is the daughter of a Dutch father and a Canadian mother. In the first weeks of her life she contracted meningitis, resulting in a severe sickness that lasted a few months. Her parents were told she was not going to survive. Growing up, Vandervoort was involved in several sports such as football, karate (second-degree black belt), basketball, tennis, gymnastics, and baseball. She has a sister named Sarah and she is related to Canadian actor Gordon Pinsent.
She started her career at the age of 13. After taking several classes and doing background work on Canadian shows such as Road to Avonlea and Harriet the Spy, she got her first speaking role in the Canadian children's series Goosebumps and Are You Afraid of the Dark?.
After commercials and guest-starring roles in Mutant X, Prom Queen: The Marc Hall Story, Goosebumps, Twice in a Lifetime, Doc, Sue Thomas: F.B.Eye, Troubled Waters, The Dresden Files, and a few Disney Channel original movies (Mom's Got a Date with a Vampire and Alley Cats Strike), at age 19, while attending York University where she studied Psychology and English, Vandervoort landed a lead role as Sadie Harrison on the CTV teen drama Instant Star, which ran for four seasons.
In 2006, Vandervoort shot her first feature titled The Lookout with Jeff Daniels, Joseph Gordon-Levitt, Matthew Goode and Isla Fisher. Several other TV appearances such as CSI: Crime Scene Investigation led Vandervoort to the role of Clark Kent's Kryptonian cousin "Kara Kent" (the woman destined to become Supergirl) on The CW serial drama Smallville. She was a regular in season seven, and appeared in the "Bloodline" episode for season eight. She then returned for another two episodes in the 10th and final season of Smallville.
Following The CW and Smallville, Vandervoort then shot the sequel to the feature film Into the Blue titled Into the Blue 2: The Reef. She next filmed an independent production titled The Jazzman, which also starred Canadian stars Michael Ironside (who appeared in the second V mini-series as well as the 1984 V regular series) and Corey Sevier.
Vandervoort portrayed "Lisa", an extraterrestrial Visitor, in the 2009 ABC science fiction series V, a reboot of the 1980s science fiction franchise of the same name.
In 2010, Vandervoort appeared in the two-part miniseries Riverworld in which she plays Jessie Machalan, the fiancée of war correspondent Matt Ellman who wakes up after death on a planet populated by everyone who has ever lived on Earth. In 2011, she starred in the thriller The Entitled, alongside Ray Liotta and Kevin Zegers.
In October 2011, she posed for PETA as part of the "Exotic Skins" campaign and in 2014, she appeared nude again for an ad that protested against the keeping of marine mammals in captivity. In 2012, she had a small role in Seth MacFarlane's hit comedy film Ted, playing Mark Wahlberg's coworker Tanya.
In 2014, she appeared in the TV adaptation of the Kelley Armstrong novel Bitten, which premiered on January 13, 2014.
In 2016, Vandervoort appeared as the supervillain Indigo/Brainiac 8 in three episodes of season one of the CBS action-adventure series Supergirl.