Stam was born in Kincardine, Ontario, and grew up on a farm alongside her six brothers. As a child, her family was very religious, practicing the Christian faith. She originally wanted to be a dentist. Stam was discovered in a local Tim Hortons coffee shop by Michele Miller, an agent at the International Model Management agency in Barrie, Ontario, who found Stam on the way back from Canada’s Wonderland, a theme park just outside Toronto. Stam attended St. Joseph’s High School in Barrie, Ontario, where she lived with roommate and fellow model Michelle V.
As soon as photographer Steven Meisel discovered the then 16-year-old Stam, he cast her in every ad campaign of his, and suddenly she was a star. “I guess I’m his muse,” she has said of her mentor Stam won the Los Angeles Model Look Search in 2002. Her career was set off when she appeared on the cover of UK & German Vogue and she has appeared in advertisements for Marc Jacobs, Anna Sui, Vera Wang, Valentino, Miu Miu, Gucci, Prada, Dolce & Gabbana, Versace and Holt Renfrew. In 2004, Stam appeared in the short film Agent Orange.
Fashion designer Marc Jacobs created The Marc Jacobs Stam a bag inspired by and named after her called She also had her own featurette and opened a Theme entitled “Pink”.
In the January 2006, she appeared in the Rochas ad campaign, shot and directed by Bruno Aveillan. For Spring 2006 Ready-to-Wear, Stam walked a total of 64 shows combined during the New York, Milan, and Paris Fashion Weeks.