The 26-year-old was substituted in the second half of Saturday’s 5-0 loss at Manchester City, seemingly suffering a knee injury.
“We think it's a form of ligament damage,” Palace manager Roy Hodgson said. “I don't know quite how bad that ligament damage is.
“He's going to have a scan but it will mean he won't be playing in the next game, I'm pretty sure of that.”
Hodgson has no natural striking alternative to Benteke, the Eagles' top scorer last season with 17 goals, in his Palace squad bar Connor Wickham, who has been out since November 2016 after suffering a knee ligament injury of his own.
Frazier Campbell left on a free during the summer, a decision chairman Steve Parish has since admitted he regrets, whilst a move for Everton striker Oumar Niasse fell through on deadline day.
Winger Bakary Sako was deployed as an auxiliary striker in the 1-0 EFL Cup win over Huddersfield on Tuesday and will likely be asked to step in for the visit to Manchester United next Saturday.