Wesson was discovered at age 16 while working at a clothing store in a shopping mall. She has been featured in advertising campaigns for Thierry Mugler's Angel perfume, Christian Dior, Versace, Calvin Klein, Valentino, BCBG Max Azria, Missoni and Moschino.

She has blonde hair and blue eyes and works with the agencies Marilyn (New York and Paris), Why Not (Milan), and Modelwerk (Hamburg).

Amy Wesson has twice landed the cover of Italian Vogue and has also been on the cover of W. She was the cover girl for the Smashing Pumpkins' 1998 release Adore.

In 2001, Amy Wesson was featured in the Sports Illustrated Swimsuit Issue.