Mack, who was having one of his strongest performances of the season, was knocked out of the game in the third quarter. He rushed 14 times for 109 yards, including four runs of at least 10 yards, and a touchdown before leaving with the injury.
Jonathan Williams became the Colts' primary tailback following Mack's injury. Nyheim Hines backed him up and received snaps as the team's pass-catcher in the backfield.
Although Mack has been healthy this year, the third-year running back has struggled with injuries since entering the league in 2017. He was impacted by hamstring and foot ailments, along with a concussion, in 2018, which limited him to only 12 games.
In nine games this season, Mack has 178 carries for 753 yards and three touchdowns. He has added 12 receptions for 76 yards.
The Colts beat the Jaguars 33-13 on Sunday, moving to 6-4 this season. Indianapolis will play the Houston Texans on Thursday Night Football.