Due to his success with Libourne Saint-Seurin, Valbuena services were in high demand. On June 9, 2006, his dream move to Ligue 1 was complete securing a move to French giants Olympique de Marseille agreeing to a three-year deal.

Mathieu's start with Marseille got off to a bad start picking up an injury while training that same summer. Due to the injury, he made his debut late in the season against Valenciennes coming on as a substitute in their 1–0 victory. He made 14 more appearances that season, mainly as a substitute, including a match where he scored his first goal for Marseille, a game-winner in the 86^th minute against Saint-Étienne.

The following season saw a drastic improvement from Valbuena, primarily due to him staying healthy and the departure of Franck Ribéry. His playing time increased and he displayed amazing form including scoring a wonder goal in a UEFA Champions League group stage match against English powerhouse Liverpool at Anfield. The goal would turn out to be the game-winner with Marseille upsetting Liverpool 1–0.

Due to his promising performances, Marseille awarded him a contract extension, which will keep him with the side until 2010. He signed a new extension in April 2008, which ties him to the club until 2013.