He was named as an All-Australian at the 2007 NAB AFL U18 Championships. He was drafted by Melbourne in the 2007 National Draft at pick 14, but was placed on the long term injury list due to stress-related back problems. He made his debut in the final game of the 2008 AFL season but suffered a further back injury in the early part of the 2009 season.
He returned in round 7 and played eleven games in 2009, including Round 14 against West Coast when he was awarded three Brownlow Medal votes and was nominated for the AFL Rising Star award.
Jack Grimes suffered a season-ending injury in the round 7 match against the West Coast Eagles.
On 3 February 2012 he was named, alongside fellow youngster Jack Trengove as the co-captain of Melbourne Football Club. At 22 years of age he will be one of the youngest ever captains in VFL/AFL history.