Flamini signed a contract with Milan on 5 May 2008 worth €5.6 million per season over a four year period. Flamini wore the number 84 on his jersey to represent his year of birth. He made his Serie A debut on August 30, 2008 in a 2-1 loss to Bologna.

In the first half of the season, Flamini did not enjoy the number of starts or appearances in the ageing Italian team as he enjoyed in his last season at Arsenal, and was regarded as a utility player at A.C. Milan as he was in his first few years at Arsenal. However in the second half of the season, injuries to other players and consistent good form helped him to cement a starting place in the side. With Milan ailing to find a stable defence and a lack of a fit, consistent and reliable right back, Gianluca Zambrotta was switched to the opposite side to help Flamini earn a place as a tenacious right back.

For the 2009-10 season he will now wear number 16, like he did at Arsenal, rather than his year of birth 84.