Son of horse breeders, the young man spent his childhood in the countryside near Paris. In his youth, Guillaume wanted to be a horse-rider, and briefly followed a professional career in the sport. A bad fall broke his dreams, but is at the origin of his acting career, and success. After briefly studying acting, he started his career. Eclectic and moving, Canet is also a successful director, he has directed movies like Ne le dis à personne (2006) and Les petits mouchoirs (2010)

In 2015, after 20 years of career, he received his first important nod as an actor for playing a serial killer in La prochaine fois je viserai le coeur (2014). He was nominated to Cesar Awards but eventually lost to Pierre Niney. Before that, he received a nod as Breakout Actor in 1998.