The 38-year-old Manning, beginning his 17th season after throwing for an NFL-record 55 touchdowns last year, completed 12 of 14 passes for 102 yards and a 120.8 rating. He was 8 for 8 on Denver's second drive, then backup Brock Osweiler took over and threw for a score and led another touchdown drive in a preseason matchup of the past two Super Bowl losers.
Colin Kaepernick went 5 for 9 for 39 yards in his two series before a sellout crowd at the team's flashy new digs in the heart of Silicon Valley. Major League Soccer's San Jose Earthquakes beat the Seattle Sounders in the stadium's first sporting event Aug. 1.
Demaryius Thomas had three catches on Denver's opening drive, including a 20-yard gain. That gives Thomas 10 receptions for 89 yards in Denver's two victories against the NFC West's powerhouses, the Super Bowl champion Seattle Seahawks and San Francisco.
C.J. Anderson ran for a 1-yard TD, while Matt Prater kicked a 26-yard field goal and Mitch Ewald added a late 22-yarder. San Francisco's typically spot-on Phil Dawson sailed two long kicks wide right.
Denver did it on defense, too, getting two interceptions and a fumble recovery and a goal-line stand to end the game. The Broncos recovered another fumble on special teams.
The 49ers lost safety Antoine Bethea to a concussion early in the second quarter. He was able to walk off on his own, but later left for the locker room.
Denver linebacker Lamin Barrow limped off early in the second half with a lower leg injury, then the Broncos lost tight end Gerrell Robinson to a knee injury.
As San Francisco struggled in all phases, tens of thousands of fans made their way out midway through the third quarter — certainly helping to alleviate traffic concerns. The 49ers ended a four-decade run at Candlestick Park last season.
Two key members of San Francisco's offense made their first appearances of the preseason, with Frank Gore running for 9 yards on the first of his two carries. Wide receiver Michael Crabtree also appeared as defensive stars Patrick Willis and Justin Smith got the day off.
Broncos cornerback Kayvon Webster missed the game after spraining an ankle during Saturday's practice. Denver already was thin as Chris Harris Jr. returns from tearing his left anterior cruciate ligament during the playoffs.
Linebacker Von Miller, who tore his right ACL in Week 16, could still play in the preseason, while that is unlikely for Harris. Denver remains without running back Montee Ball, who is working back from an appendectomy earlier this month.
Kaepernick had his chances during his brief stint on the field.
On third-and-4 from the 37, Kaepernick barely overthrew Brandon Lloyd in the end zone. Dawson then missed his first field goal attempt in the new stadium, sending a 55-yarder wide right. He missed wide right again from the other end on a 44-yarder late in the first half, and these weren't in the unpredictable elements of Candlestick.
The 49ers are scoreless in their last seven quarters and have been outscored 57-3 this preseason. They lost 23-3 at Baltimore on Aug. 7.
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