The Bolts erased a 22-point deficit in the second half to pull within eight points of tying the game, but Philip Rivers and the offense couldn't put together a scoring drive on their last possession of the game. Manning wound up throwing four touchdown passes while Rivers was held to just one.
Here are today's takeaways from a tough loss at home in what was a must-win game for the Chargers, who may or may not be in a position to contend for a playoff spot.
Manning has been downright perfect this season, and it was no secret that the key to slowing down this Broncos offense was going to be pressuring the quarterback.
Manning has been sacked just 13 times on the season after Sunday's game as the Chargers defense managed to reach the savvy quarterback just twice. Larry English had the first and Tourek Williams had the second, which resulted in a forced fumble.
With the time he was given, Manning had another monster game against a bad secondary. It was the fourth time this season he's thrown four TDs in a game.
It should come as no surprise that Manning was going to obliterate San Diego's secondary, but the personnel struggles continue to linger for defensive coordinator John Pagano.
For the second straight week, Derek Cox was benched during a game for poor play. The free-agent pickup from Jacksonville failed to push Julius Thomas out of bounds on the Broncos' first score of the game, which led to the switch at cornerback.
Cox would eventually reenter the game, but the secondary struggled as a whole to deal with the size and speed of both Julius and Demaryius Thomas. The two of them combined for four TD catches and 204 yards.
Keeping the offensive line healthy is proving to be a bigger challenge than San Diego expected as two starters went down with injuries on Sunday.
King Dunlap suffered a concussion, his third this season, and did not return to the game, while Nick Hardwick suffered a stinger and did try to reenter to the game, but to no avail as he was forced to come out.
The Chargers had only seven O-linemen active against the Broncos, and all seven eventually ended up playing. Depending on the severity of these injuries, this could be disastrous for Rivers, who was sacked four times.
Keenan Allen's hot start to his rookie year hit a snag as he went up against a very physical Denver secondary.
Allen was limited to four catches for 41 yards despite gaining over 100 yards in three of his last four games. With Allen contained, Antonio Gates benefited with four catches for 62 yards.
Denver came into the game with the 30th-ranked pass defense in yards allowed per game (299.1), but the individual efforts to lock down the Chargers' playmakers were solid.
After missing three straight games with a groin injury, Donald Butler made his long-awaited return on defense and put forth a worthy effort in the Chargers' loss.
Butler recorded seven tackles and a fumble recovery in his first game back. The good news is that Butler is still a playmaker on defense who can come up with turnovers and game-changing plays, but the bad news is that the rest of the defense was unable to follow suit.
With the Broncos opting to throw more, it was hard for the front seven to get involved, but the usual suspects had good individual performances (Eric Weddle, Manti Te'o, Kendall Reyes).
In last week's loss to Washington, it was a topic of debate as to why Ryan Mathews didn't see a carry on the Chargers' final drive near the goal line in regulation.
Mathews finished with 34 yards on seven carries against the Redskins, but finished with 59 yards on 14 carries with a score, his second of the year, near the goal line in the fourth quarter against Denver. It was clear the Chargers coaching staff made the effort to double Mathews' carries, and it worked for the most part, but Mathews had trouble staying in the game due to injury.
The Chargers had the ball for 38:03 compared to the Broncos' 21:57, and the Chargers even ran more plays than the Broncos, but efficiency was the difference between the two.
Denver was a perfect 2-of-2 in the red zone and 3-of-8 on third-down. San Diego, meanwhile, went 2-of-4 in the red zone and 7-of-16 on third down.
San Diego lost the game because it settled for a field goal against one of the league's best offenses. In the overtime loss to Washington last week, the Chargers struggled with the same problem, and that trend seems to be continuing.