Published: Sep 17, 2012 1:16 AM EDT
Updated: Sep 17, 2012 6:32 AM EDT

SAN FRANCISCO (AP) - Matthew Stafford stumbled at the start again and the Detroit Lions never could recover against one of the NFL's best defenses.

Stafford threw his fourth interception in two games while passing for 230 yards and a touchdown, and the Lions lost 27-19 to the San Francisco 49ers on Sunday night.

"It's one thing if we come out here and play our best football and get blown out of the water," said Stafford, who threw three first-half interceptions in a Week 1 win against St. Louis. "We played poorly."

The 49ers finally made Stafford pay for the mistakes.

San Francisco's stingy, opportunistic defense again showed why it's one of the league's fiercest. A week after shutting down Aaron Rodgers and the Green Bay Packers' prolific offense at Lambeau Field, Stafford became the latest quarterback foiled by Jim Harbaugh's bunch.

Vernon Davis caught touchdown passes of 21 and 23 yards from Alex Smith, and a September showdown of NFC playoff contenders hardly lived up to its hype.

Stafford finished 19 for 32 passing and missed a chance to become the first player in NFL history to throw for 350 yards in five straight games. Drew Brees of the Saints also did so in four consecutive games last season.

"I don't think as an offense we've hit our stride yet," Stafford said. "We moved the ball really well at times today against a really good defense, and we didn't take advantage of our opportunities in the red zone like we need to. Against a good team like that, every point counts and every point is crucial. Too many times we were kicking field goals at the end of drives. It's unlike us, and we understand that."

Instead, Stafford was outplayed by another former No. 1 overall pick.

Smith completed 20 of 31 for 226 yards and extended his franchise-record streak of passes without an interception to 216. He led the reigning NFC West champion Niners (2-0) to their ninth straight win in the series since the Lions' last victory on Sept. 25, 1995.

San Francisco ran its home winning streak against the Lions to 12 games since Detroit's last victory at Candlestick Park on Nov. 2, 1975.

And no heated greeting after this one.

Harbaugh and Lions coach Jim Schwartz met each other with a friendly hello and handshake during pregame warmups, then an uneventful shake and half-hug when time expired. That was far different from last year, when Harbaugh's hard handshake and backslap sent Schwartz chasing after him in a wild scrum.

This time, the Lions' lousy play was the only thing Schwartz was upset about.

"We didn't do a job enough job in anything," Schwartz said. "Whether it was the run game, the pass game, defense, special teams. We need to play better in all phases. We left a lot of opportunities on the field."

Calvin Johnson caught eight passes for 94 yards but wasn't even a factor as the Lions (1-1) never got closer than the 20 until their final drive on a cool, windy night by the bay. San Francisco's secondary kept Megatron from catching a touchdown pass for the second straight matchup, forcing Stafford to rely heavily on the running game.

Frank Gore also carried 17 times for 89 yards and a 1-yard touchdown for San Francisco.

"It wasn't our worst game, but we didn't have our best game," Johnson said. "We were still in the game. There are some things to take from this that are good. There are some things to learn from, too. It's a tough one."

Just another impressive outing by a defense that shut down Rodgers in a 30-22 win over the Packers last week at Lambeau Field.

Jason Hanson finished with field goals of 38, 41, 40 and 48 yards for Detroit. He also missed one off the right upright on a 40-yard attempt late in the second quarter. The Lions scored their lone touchdown on Stafford's 9-yard TD pass to Brandon Pettigrew with 1:29 remaining.

After Hanson's first field goal, Kendall Hunter of the 49ers fumbled the kickoff return after being stripped by Tahir Whitehead and Kassim Osgood recovered. It marked the first career lost fumble in 18 games for the second-year halfback.

But Ahmad Brooks batted down a pass on third down in the ensuing series as the Lions had to settle for another field goal.

San Francisco's defense delivered again on Detroit's next series. On third-and-6 from the 20, Stafford threw down the middle of the field with nobody even close and safety Dashon Goldson jumped in for an interception.

A special teams blunder hurt the Lions late in the first quarter when Drayton Florence, another fill-in cornerback, was flagged for running into Akers. That gave the Niners first down at the 12, and Gore scored three plays later 3 seconds into the second quarter.

San Francisco's defense kept Detroit out of the end zone on the Lions' first drive despite a big penalty. Chris Culliver received a debated pass interference call from the replacement officials when he tipped a pass intended for Titus Young for a 33-yard penalty.

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Antonio Gonzalez can be reached at: www.twitter.com/agonzalezAP