ORCHARD PARK, N.Y. - A second consecutive cross-country trip and early start seemed to doom the Rams.
They came out flat on Sunday, made mistakes and trailed the Buffalo Bills by 25 points early in the third quarter.
The Rams stayed poised, forced two key turnovers and came back to take the lead, but they could not hold off the Bills at the end.
Josh Allen's fourth touchdown pass, in the final 30 seconds, sent the Rams to a 35-32 defeat at Bills Stadium.
Rams quarterback Jared Goff passed for 321 yards and two touchdowns, Darrell Henderson rushed for a career-high 114 yards and a touchdown, and the Rams got several big defensive plays but they fell short of starting 3-0 for the third consecutive season.
John Johnson's interception gave the Rams an opportunity to start a run of 29 unanswered points. Star defensive tackle Aaron Donald forced a fumble that he recovered, setting up the Rams' go-ahead touchdown.
But Allen completed several clutch third-down throws and a pass interference penalty against cornerback Darious Williams ultimately doomed the Rams.
The Rams trailed, 21-3, at halftime after Allen passed for two touchdowns and ran for another.
It didn't get any better for the Rams at the start of the second half.
Their first possession ended with Goff's fourth down pass at the 48-yard line falling incomplete.