The Ravens were in trouble on their first play from scrimmage. Lamar Jackson left after an incompletion, injuring his right thumb.
The Ravens also lost backup Tyler Huntley to a toe injury in the first half, leaving undrafted rookie Joe Fagnano, the emergency third quarterback, to make his NFL debut.
Baltimore had no chance, losing to Josh Allen and the Bills 36-10.
Buffalo moves to 6-1, and the Ravens fall to 4-4.
The Bills led start to finish, outgaining the Ravens 426 to 144.
Josh Allen was 21-of-34 for 289 yards with two touchdowns and an interception. He also ran seven times for 30 yards and a touchdown.
James Cook has 21 carries for 80 yards and a touchdown, and Dalton Kincaid caught four passes for 86 yards and a touchdown. DJ Moore caught four passes for 82 yards and a touchdown but also lost a fumble.
Fagnano went 10-of-21 for 91 yards and an interception, and Derrick Henry had 11 carries for 53 yards and a touchdown.