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 Tell No One (2006) and Little White Lies (2010)

In 2015, after 20 years of career, he received his first important nod as an actor for playing a serial killer in Next Time I'll Aim for the Heart (2014). He was nominated to Cesar Awards but eventually lost to Pierre Niney. Before that, he received a nod as Breakout Actor in 1998.