49ers 45, Bills 3: Alex Smith passed for 303 yards and three touchdowns and Frank Gore added 106 yards and a touchdown on the ground as San Francisco dominated visiting Buffalo.
Smith was 18-for-24 and compiled a 156.3 quarterback rating in recording better than 300 yards passing for only the third time in his career - and the first time in a victory. He also had 49 yards on three rushes, helping the 49ers to a franchise-record 621 total yards - breaking the previous mark of 598 set against the Bills in 1992.
San Francisco (4-1) was equally dominant on defense, holding the Bills (2-3) to 204 yards and forcing two turnovers. The 49ers have outscored their opponents 79-3 in the past two games.
Michael Crabtree caught six passes for 113 yards and a touchdown, and Vernon Davis had five catches for 106 yards for the 49ers. Kyle Williams and Mario Manningham also caught touchdown passes, and Colin Kaepernick and Anthony Dixon had touchdown runs.
The Bills crossed midfield only twice, resulting in Rian Lindell's 31-yard field goal in the first quarter and Chris Culliver's interception of a Ryan Fitzpatrick pass in the third quarter. Fitzpatrick was 16-of-26 for 126 yards.
GAME NOTEBOOK: The 49ers had a 300-yard passer, a 100-yard rusher and two 100-yard receivers for the first time since 1961. … Smith's longest completion in the first four games of the season was 29 yards. He had completions of 53, 36 and 43 yards on Sunday. … The Bills have allowed 138 points in their three losses.