San Francisco, CA (Sports Network) - Alex Smith was nearly perfect through the air, Frank Gore had his way on the ground and the San Francisco 49ers defense again kept the opposition out of the end zone in a 45-3 shellacking of the Buffalo Bills.
Smith connected on 18-of-24 passes for 303 yards and three touchdowns, while Gore ran for 106 yards and a score on 14 carries for the 49ers (4-1), who gained a franchise-record 621 yards in their second straight blowout victory.
San Francisco beat the Jets in New York, 34-0, in Week 4 and scored the final 42 points Sunday to win going away.
Michael Crabtree caught six passes for 113 yards and a TD, and Vernon Davis added 106 yards on five receptions in the rout.
Ryan Fitzpatrick finished with just 126 yards and an interception for Buffalo (2-3), which came in with an NFL-high 16 touchdowns but gained just 10 first downs in its second straight debilitating loss.
The Bills gave up 45 second-half points in last week's loss to the Patriots.