At 6-6, the Rams are tied with the Cardinals and behind the 7-5 Seahawks in the NFC West, so they need the win to stay competitive for a postseason berth.
That won't be easy against the 10-2 Bills, now on a seven-game winning streak that commands respect from the Rams coaching staff.
"Complete offense," said Rams head coach Sean McVay. "They have the ability to do a lot of things. He does a great job getting all his playmakers involved."
Key to the game will be slowing down quarterback Josh Allen, seen as a potential MVP candidate this season. In 12 games, Allen has thrown for 20 touchdowns and just five interceptions.
"It's incredible what he's able to do," said Rams quarterback Matthew Stafford. "I remember him jumping over linebackers in Minnesota, doing all kinds of stuff. He's as physically talented of a runner at quarterback as I've seen."
If there's a weakness to this Buffalo squad, it might be defense against the run, giving up 123 yards a game. That's a good sign for the Rams, who ran for 156 yards and a touchdown in their 21-14 win over the Saints last Sunday.