San Francisco —  

Chan Gailey had few words and few ways to describe what he had just witnessed.

The beleaguered Buffalo Bills and their baffled coach walked out of Candlestick Park on the wrong side of another lopsided game and another San Francisco 49ers record — and quite a few others, too.

A week after allowing 45-second half points to the New England Patriots, the Bills hit a new low. Buffalo allowed a franchise-record 621 yards, losing 45-3 to San Francisco on Sunday.

"I have no answers and no excuses," Gailey said. "I don't have the answers and I have to find the answers. That's my job."

Alex Smith threw for a season-high 303 yards and three touchdowns, and Frank Gore ran for 106 yards and a score as San Francisco surpassed its own franchise mark. The team's previous best was 598 yards in a 34-31 loss to the Bills on Sept. 13, 1992, which also had been Buffalo's worst.

Michael Crabtree (seven catches for 113 yards) and Vernon Davis (seven catches for 106 yards) each eclipsed the century mark as San Francisco (4-1) became the first team in NFL history with 300 yards passing and 300 yards rushing. Even Randy Moss, rarely targeted in his comeback, caught a pass for 11 yards.

Smith, the 2005 No. 1 overall pick out of Utah, threw TD passes of 43, 28 and 10 yards and exceeded 300 yards passing for only the third time in his career — and first in a victory. The last time came when he had 309 yards passing in a loss at Philadelphia two years ago — "a completely different world," he said — in coach Mike Singletary's final season.

"Quarterback was near perfect," new coach Jim Harbaugh said.

Even for a franchise that knows disappointment, never has Buffalo had such a horrendous two-week stretch.

The Bills allowed 580 total yards in that humiliating 52-28 home loss to New England last week. Beginning a two-game road trip, Buffalo's baggage also traveled to the West Coast.

Rian Lindell kicked a 31-yard field goal in the first quarter before the 49ers scored the final 42 points to hand Buffalo (2-3) its second straight embarrassing loss.

Ryan Fitzpatrick threw for 126 yards and an interception, and the Bills rushed for only 89 yards, most with the game well out of hand once again.

Since taking a 21-7 lead against the Patriots, Buffalo has been outscored 90-10. The Patriots and 49ers combined to gain 1,201 yards, and the Bills became the first team to give up at least 550 yards in consecutive games in the same season since the 1950 New York Yanks.

"They flat-out dominated the game from end to end," Fitzpatrick said. "We just got beat bad by a better team today. There was no fancy stuff. They are who they are and they just played better."

Far better.

With the Bills unable to slow anybody down on defense, San Francisco abandoned its usually conservative game plan to deliver a scintillating show in the air.

Smith, who sprained his middle finger in the fourth quarter, completed 18 of 24 passes. He also had a perfect 158.3 passer rating in the first half, when he threw for 237 yards — a career best for a half.

The longest completion Smith had in the first four weeks was for 29 yards. In the first half alone, he completed a 53-yarder to Davis that set up a field goal by David Akers, a 43-yard touchdown to Kyle Williams and hooked up with Crabtree for 36 yards.

Williams took the back-shoulder pass from Smith, spun away from a defender and ran the final 10 yards free into the end zone. Williams fell to his knees, raised his arms and nodded to the sun-splashed crowd at Candlestick Park after giving the 49ers a 10-3 lead.

Every time the Bills blew an opportunity — and they blew plenty — the 49ers capitalized.

Backup quarterback Colin Kaepernick, who ran for 39 yards on four carries, fumbled on an end-around and Buffalo took over at its own 17. Two plays later, Patrick Willis stripped Scott Chandler, San Francisco recovered and Smith floated a 28-yard touchdown to Crabtree to put the 49ers in front 17-3 with 24 seconds to go before the half.

"We have to figure out what in the world is going on from the first guy to No. 11 on defense," said defensive end Mario Williams. "It's all on us."

A holding penalty on Buffalo's Jairus Byrd wiped out a punt return Leodis McKelvin took for a touchdown in the first quarter. The offense failed to score any points after McKelvin returned a kickoff 59 yards. And after a 12-play, 75-yard drive that took nearly 6 minutes stalled in the second quarter, Lindell kicked a field goal for Buffalo's only score.

Smith led another touchdown drive that featured Kaepernick gaining 15 yards on a sweep and ended one play later when Gore dove over the pile for a TD that extended San Francisco's lead to 24-3.

Chris Culliver intercepted an underthrown pass by Fitzpatrick just shy of the goal line to end Buffalo's best chance to reach the end zone all afternoon.

Smith also tossed a 10-yard TD pass to Mario Manningham, Kaepernick ran 16 yards for a score and Anthony Dixon added a 3-yard run for the final touchdown.

Buffalo, which snapped an eight-game road losing streak with a Week 3 win at Cleveland, started a string of four five on the road with another setback. The Bills will practice in Arizona next week to get ready for the Cardinals instead of traveling back East, similar to what the 49ers just did staying in Ohio between games at Minnesota and New York.

"After last week, I would have bet anything that we wouldn't have come out and played like this," linebacker Nick Barnett said. "It's disappointing and deflating. It's very stunning. I would not have ever imagined being in this situation with this defense."