Grimes was subbed out during the third quarter of the Demons' dire performance against Greater Western Sydney on Sunday with the injury.
He had missed the previous two weeks with another hamstring injury but had managed 18 games for the season, his second highest single season games tally in an injury-plagued career.
Grimes, 25, has enjoyed just 18 wins in 86 games but has been a relatively consistent performer during the past three seasons.
Melbourne's elite performance manager David Misson told the club's website that Grimes re-injured his hamstring during the GWS game.
He said scans revealed the tear was not bad, but it ruled the co-captain out for the final two weeks.
"The scan revealed a similar area and a similar-sized tear and it was not too bad, but it’ll mean that he won’t play again this season," Misson said.
In better news, midfielder Jack Trengove pulled up well after having his first run on the AlterG treadmill on Monday.
Trengove – who took a mid-season break overseas after breaking the navicular bone in his left foot – is expected to spend two to three weeks on the treadmill before resuming running outside.
