Freeman suffered the injury in an 18-12 season-opening loss at Philadelphia. The two-time Pro Bowler said after the game he was fine but did not practice all week.
Coach Dan Quinn said it's the same knee Freeman hurt last season, but Quinn said there was no structural damage. Quinn didn't give timetable but is hopeful it won't be long term.
The Falcons will start Tevin Coleman at running back with Freeman sidelined. Coleman's career rushing numbers against the Panthers include 36 carries for 152 yards with a touchdown, six first downs and a long run of 55 yards.
Falcons offensive coordinator Steve Sarkisian discussed the need to establish Coleman and the running game against a strong Panthers run defense, led by linebacker Luke Kuechly.
"At the end of the day, you got to just keep chipping away at them,'' Sarkisian said. "I think we've got a good plan going into it. We can't become a one-dimensional team against this group, because it can rush the passer really well. They've got great blitz packages. Balance is going to be key, but we've got to make the most of our runs when we're calling them."
The Falcons ran the ball just 18 times for 74 yards in the season-opening loss to the Eagles while Matt Ryan attempted 43 passes.
With Freeman out, rookie Ito Smith moves up the depth chart behind Coleman. The Falcons also elevated Brian Hill from the practice squad, and Hill is expected to be active as the third running back and also play on special teams.
Freeman, a two-time Pro Bowler, rushed for 865 yards and seven touchdowns on 196 carries in 2017. He had back-to-back, 1,000-rushing-yard seasons in 2015 and 2016. Last year, a significant right knee injury limited Freeman's production.