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 Mich�le Miller, an agent at the International Model Management agency in Barrie, Ontario, who found Stam on the way back from Paramount Canada's Wonderland, a theme park just outside Toronto.
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 German Vogue and she has appeared in advertisements for Marc Jacobs, Anna Sui, Vera Wang, Valentino, Miu Miu, Gucci, Prada, Dolce & Gabbana, and Holt Renfrew. In 2004, Stam appeared in the short film Agent Orange.
After she dyed her hair blonde on a whim during the summer of 2005, she was cast for 54 shows. Good friend and fashion designer Marc Jacobs recently created a bag inspired by and named after her (The Marc Jacobs Stam). Stam is currently the face of Armani, Sonia Rykiel, BCBG, and Rochas for 2006. She also appeared in the 2006 Victoria's Secret Fashion Show.
Stam previously dated Anthony Kiedis of the Red Hot Chili Peppers. In January of 2006 she was photographed topless while frolicking with Kiedis on the Caribbean island of St. Barts. On January 12, 2006 she was photographed with him during a Los Angeles Lakers/Cleveland Cavaliers basketball game at the Staples Center in Los Angeles. Before Kiedis, Stam dated Harrison Ford's son, Malcolm.