Originally hailing from Springdale, Newfoundland, Henstridge grew up in Fort McMurray, Alberta, Canada. Leaving home at 14 to pursue a modeling career, she moved to Paris, eventually becoming successful enough to grace the cover of French Cosmopolitan when she was only 15. Henstridge also appeared in ads for Oil of Olay and Lady Stetson, but she soon realized that she was meant for a more creatively stimulating calling. Whether her starring role in Species could be deemed creatively stimulating is arguable, but it did provide Henstridge with her breakthrough. Unfortunately, she next opted for near-nonentity status in such critical missteps as the Jean-Claude Van Damme vehicle Maximum Risk (1996) and Species II (1998), which was nowhere near as commercially successful as its predecessor.

Henstridge broke into new territory with the romantic comedy Dog Park (1998), co-starring alongside Janeane Garofalo and Luke Wilson. She continued to flex her comedic muscles in 2000 with The Whole Nine Yards, sharing the screen with a cast that included Matthew Perry, Bruce Willis, and Michael Clarke Duncan. Later that year, she appeared in Bounce, a romantic drama about a man (Ben Affleck) who falls in love with the widow (Gwyneth Paltrow) of the plane crash victim to whom he had given his seat on a doomed airplane.