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Photo: Justin Edmonds / Getty Images Image 1 of / 34 Caption Close Image 2 of 34 Quarterback Colin Kaepernick #7 of the San Francisco 49ers hangs his head in the third quarter. Quarterback Colin Kaepernick #7 of the San Francisco 49ers hangs his head in the third quarter. Photo: Justin Edmonds / Getty Images Image 3 of 34 Wide receiver Demaryius Thomas catches a touchdown pass from Peyton Manning under coverage by cornerback Tramaine Brock. The touchdown was Manning's 509th career touchdown pass. Wide receiver Demaryius Thomas catches a touchdown pass from Peyton Manning under coverage by cornerback Tramaine Brock. The touchdown was Manning's 509th career touchdown pass. Photo: Justin Edmonds / Getty Images Image 4 of 34 Denver Broncos quarterback Peyton Manning celebrates his 509th career touchdown pass with teammates during the first half. Denver Broncos quarterback Peyton Manning celebrates his 509th career touchdown pass with teammates during the first half. Photo: Jack Dempsey / Associated Press Image 5 of 34 Image 6 of 34 Linebacker Aaron Lynch congratulates quarterback Peyton Manning #18 of the Denver Broncos on his NFL-record 509th career touchdown pass. Linebacker Aaron Lynch congratulates quarterback Peyton Manning #18 of the Denver Broncos on his NFL-record 509th career touchdown pass. Photo: Justin Edmonds / Getty Images Image 7 of 34 Head coach Jim Harbaugh of the San Francisco 49ers has a word with Colin Kaepernick #7 during a game against the Denver Broncos. Head coach Jim Harbaugh of the San Francisco 49ers has a word with Colin Kaepernick #7 during a game against the Denver Broncos. Photo: Doug Pensinger / Getty Images Image 8 of 34 San Francisco 49ers quarterback Colin Kaepernick scrambles against the Denver Broncos. San Francisco 49ers quarterback Colin Kaepernick scrambles against the Denver Broncos. Photo: Jack Dempsey / Associated Press Image 9 of 34 San Francisco 49ers wide receiver Stevie Johnson (13) scores a touchdown against the Denver Broncos during the first half. San Francisco 49ers wide receiver Stevie Johnson (13) scores a touchdown against the Denver Broncos during the first half. Photo: Jack Dempsey / Associated Press Image 10 of 34 Image 11 of 34 San Francisco 49ers quarterback Colin Kaepernick scrambles against the Denver Broncos. San Francisco 49ers quarterback Colin Kaepernick scrambles against the Denver Broncos. Photo: Jack Dempsey / Associated Press Image 12 of 34 San Francisco 49ers center Daniel Kilgore (67) is carted off the field after being injured. San Francisco 49ers center Daniel Kilgore (67) is carted off the field after being injured. Photo: Jack Dempsey / Associated Press Image 13 of 34 San Francisco 49ers quarterback Colin Kaepernick is hurried against the Denver Broncos during the first half. San Francisco 49ers quarterback Colin Kaepernick is hurried against the Denver Broncos during the first half. Photo: Joe Mahoney / Associated Press Image 14 of 34 Wide receiver Wes Welker is forced out of bounds at the goal line by strong safety Antoine Bethea. Wide receiver Wes Welker is forced out of bounds at the goal line by strong safety Antoine Bethea. Photo: Justin Edmonds / Getty Images Image 15 of 34 Image 16 of 34 Denver Broncos quarterback Peyton Manning throws against the San Francisco 49ers during the first half. Denver Broncos quarterback Peyton Manning throws against the San Francisco 49ers during the first half. Photo: David Zalubowski / Associated Press Image 17 of 34 San Francisco 49ers wide receiver Anquan Boldin (81) bobbles a pass before catching it as Denver Broncos cornerback Bradley Roby (29) defends during the first half. San Francisco 49ers wide receiver Anquan Boldin (81) bobbles a pass before catching it as Denver Broncos cornerback Bradley Roby (29) defends during the first half. Photo: Brennan Linsley / Associated Press Image 18 of 34 San Francisco 49ers head coach Jim Harbaugh, right, argues with referee John Parry. San Francisco 49ers head coach Jim Harbaugh, right, argues with referee John Parry. Photo: Joe Mahoney / Associated Press Image 19 of 34 San Francisco 49ers running back Frank Gore, right, is hit by Denver Broncos defensive end Quanterus Smith (93) during the first half of an NFL football game, Sunday, Oct. 19, 2014, in Denver. (AP Photo/Jack Dempsey) less San Francisco 49ers running back Frank Gore, right, is hit by Denver Broncos defensive end Quanterus Smith (93) during the first half of an NFL football game, Sunday, Oct. 19, 2014, in Denver. (AP Photo/Jack ... more Photo: Jack Dempsey / Associated Press Image 20 of 34 Image 21 of 34 Denver Broncos wide receiver Emmanuel Sanders (10) pulls in a pass as San Francisco 49ers inside linebacker Chris Borland (50) and Tramaine Brock (26) defend during the first half. Denver Broncos wide receiver Emmanuel Sanders (10) pulls in a pass as San Francisco 49ers inside linebacker Chris Borland (50) and Tramaine Brock (26) defend during the first half. Photo: Jack Dempsey / Associated Press Image 22 of 34 Denver Broncos running back Ronnie Hillman (23) is hit by San Francisco 49ers cornerback Tramaine Brock (26) during the first half. Denver Broncos running back Ronnie Hillman (23) is hit by San Francisco 49ers cornerback Tramaine Brock (26) during the first half. Photo: Joe Mahoney / Associated Press Image 23 of 34 San Francisco 49ers quarterback Colin Kaepernick (7) looks to pass against the Denver Broncos during the first half of an NFL football game, Sunday, Oct. 19, 2014, in Denver. San Francisco 49ers quarterback Colin Kaepernick (7) looks to pass against the Denver Broncos during the first half of an NFL football game, Sunday, Oct. 19, 2014, in Denver. Photo: Joe Mahoney / Associated Press Image 24 of 34 Denver Broncos quarterback Peyton Manning throws his 509th career touchdown pass to set the all time record during the first half. Denver Broncos quarterback Peyton Manning throws his 509th career touchdown pass to set the all time record during the first half. Photo: Jack Dempsey / Associated Press Image 25 of 34 Image 26 of 34 Denver Broncos quarterback Peyton Manning (18) throws his first touchdown of the game. Denver Broncos quarterback Peyton Manning (18) throws his first touchdown of the game. Photo: Jack Dempsey / Associated Press Image 27 of 34 Denver Broncos quarterback Peyton Manning is congratulated by San Francisco 49ers linebacker Aaron Lynch (59) after Manning threw his 507th career touchdown pass,. Denver Broncos quarterback Peyton Manning is congratulated by San Francisco 49ers linebacker Aaron Lynch (59) after Manning threw his 507th career touchdown pass,. Photo: David Zalubowski / Associated Press Image 28 of 34 Wide receiver Emmanuel Sanders celebrates a touchdown with Peyton Manning #18 and Julius Thomas #80 in the first quarter. Wide receiver Emmanuel Sanders celebrates a touchdown with Peyton Manning #18 and Julius Thomas #80 in the first quarter. Photo: Justin Edmonds / Getty Images Image 29 of 34 Wide receiver Emmanuel Sanders scores on a 3-yard touchdown pass in the first quarter. Wide receiver Emmanuel Sanders scores on a 3-yard touchdown pass in the first quarter. Photo: Justin Edmonds / Getty Images Image 30 of 34 Image 31 of 34 Fans hold a 509 sign in hopes of seeing Denver Broncos quarterback Peyton Manning set the all time touchdown passes record against the San Francisco 49ers. Fans hold a 509 sign in hopes of seeing Denver Broncos quarterback Peyton Manning set the all time touchdown passes record against the San Francisco 49ers. Photo: Joe Mahoney / Associated Press Image 32 of 34 Denver Broncos quarterback Peyton Manning throws the games' first touchdown pass during the first half. Denver Broncos quarterback Peyton Manning throws the games' first touchdown pass during the first half. Photo: David Zalubowski / Associated Press Image 33 of 34 Quarterback Colin Kaepernick #7 of the San Francisco 49ers walks in the tunnel with teammates as he prepares to face the Denver Broncos in a game at Sports Authority Field at Mile High on October 19, 2014 in Denver, Colorado. less Quarterback Colin Kaepernick #7 of the San Francisco 49ers walks in the tunnel with teammates as he prepares to face the Denver Broncos in a game at Sports Authority Field at Mile High on October 19, 2014 in ... more Photo: Justin Edmonds / Getty Images Image 34 of 34 No match for Manning: 49ers blasted 42-17 on QB's record-breaking night 1 / 34 Back to Gallery

DENVER — The 49ers had several factors working against them Sunday night: a slew of injuries, a short work week and a game against the defending AFC champions in mile-high altitude.

Oh, yeah, they also had to deal with this rather significant obstacle: Peyton Williams Manning.

Even if well-rested, at full strength and at home, the 49ers might not have been a match for the Broncos quarterback, who broke Brett Favre’s record for career passing touchdowns en route to leading Denver to a 42-17 win at Sports Authority Field.

“You can blame whatever you want to blame it on,” safety Eric Reid said. “At the end of day, we’re all professional athletes. We play for the San Francisco 49ers. We’re expected to do a job and we didn’t execute. Especially on the defensive side of the ball.”

And the opposing quarterback had plenty do with that.

In yet another virtuoso performance, Manning, 38, feasted on a banged-up defense missing All-Pro linebacker Patrick Willis, starting cornerback Chris Culliver and nickel corner Jimmie Ward. The 49ers began the game with four healthy corners, although Tramaine Brock was at less than full strength in his first game back from a turf toe injury he sustained in Week 1. They were down to three cornerbacks early in the third quarter when Chris Cook exited with a hamstring injury.

The results were predictable: Manning completed of 22 of 26 passes for 318 yards with four touchdowns before he exited with the Broncos leading by 32 after three quarters.

After making his 23rd career start, Reid laughed when asked if Manning was the best quarterback he’d faced.

“Yeah, that’s pretty easy to say,” Reid said. “I’m not sure what their coaches do, but they probably don’t have to do much. He’s out on there on the field, he recognizes the defense, he makes audibles. He does it all. You’re playing against a coordinator when you’re out there.”

On Sunday, Manning’s passer rating (157.2) was just short of perfection (158.3) and he required less than 27 minutes to collect the three touchdowns he needed to eclipse Favre’s record of 508. With the flashes of cell-phone cameras filling the stands, Manning surpassed Favre with an eight-yard strike to Demaryius Thomas with 3:09 left in the second quarter to give the Broncos a 21-3 lead.

After the score, 49ers rookie linebacker Aaron Lynch, who was 5 when Manning entered the NFL, was the first to congratulate him. Manning then tried to retrieve the record-breaking ball, but a trio of his pass-catchers – Emmanuel Sanders, Wes Welker and Julius Thomas – played keep-away from the quarterback.

It was, indeed, a laugher. In fact, in a sign the famously intense and exacting Manning was in complete command, he smiled in the huddle after he tripped over left guard Orland Franklin and was sacked on the play before his record-breaking pass.

Manning acknowledged the Broncos took advantage of defense operating at less than full-strength. Denver had 405 yards in the first three quarters and had six plays of 32-plus yards.

“They had some injuries that, I think, put some pressure on their defense,” manning said. “And we were able to take advantage of that.”

It was a grim evening for the 49ers, who allowed six sacks, had four dropped passes, allowed their longest run (37 yards) since 2010 and endured more attrition.

Already playing without All-Pro left guard Mike Iupati (concussion), center Daniel Kilgore was carted off the field in the third quarter with his left leg in an air cast. Kilgore immediately beckoned for medical assistance after linebacker Brandon Marshall crashed into the side of his leg at the end of a run by Frank Gore.

The ugliness began early.

Manning tossed touchdown passes of three yards to Emmanuel Sanders and 39 yards to Wes Welker to give the Broncos a 14-0 first-quarter lead.

Trailing 21-3, the 49ers had a must-have touchdown 11 seconds before halftime when Colin Kaepernick tossed a four-yard pass to Stevie Johnson in the back of the end zone.

On the 49ers’ first drive of the third quarter, though, Kaepernick tossed and interception, which set the stage for the other quarterback. One play after Kaepernick’s pick, Manning tossed a perfectly placed 40-yard pass to Thomas to give the Broncos a 28-10 lead.

Linebacker Ahmad Brooks said the man with the most passing touchdowns in NFL history doubles as the best quarterback he’s ever faced.

“Yeah,” Brooks said. “By far. By far. By far.”