The placement on the IR likely means the season is over for the seven-year veteran, who made 20 receptions for 272 yards and a touchdown this season.
Holmes was injured in the fourth quarter of the Jets' 34-0 loss to San Francisco Sunday. X-rays were negative but additional tests revealed a Lisfranc injury, which affects ligaments in the mid-foot.
Holmes went down after making a catch, immediately falling to the ground without being hit and fumbling. 49ers cornerback Carlos Rogers returned the fumble for a 51-yard touchdown.
The Jets signed wide receiver Jason Hill to take Holmes' roster spot.
It was the latest blow for injury-riddled New York, which also lost star cornerback Darrelle Revis with a torn knee ligament.
The Jets (2-2) play the undefeated Houston Texans Monday in East Rutherford, N.J.