As both of these AFC West rivals enter the second half of their schedule, the outcome of this game will have huge playoff implications.
For the Denver Broncos, they are trying to keep pace with the 9-0 Kansas City Chiefs in their own division, while the San Diego Chargers desperately need a win to remain in the wild card picture.
Peyton Manning and Philip Rivers have had some classic battles in the past and this is shaping up to be another West Coast shootout in San Diego.
Here are three bold predictions for Sunday afternoon's matchup.
1. Ryan Mathews rushes for 150 yards and a touchdown, and Keenan Allen does the same on the receiving side.
The Chargers were heavily criticized for their play selection at the goal line in their loss in Washington. With Mathews on the bench, they ran a draw to Danny Woodhead on first down without a fullback and lost yardage.
Two ugly incompletions later, they were forced to settle for a field goal and overtime, where they would go on to lose. Mathews has had a long history of fumbling, particularly in the red zone, but as a pure rusher, he has started to heat up in the last few weeks.
And he has not fumbled since September. The Chargers will try to establish the running game to keep Peyton Manning and the Denver offense off the field, and Mathews will be the primary recipient.
Although the Broncos have a strong run defense, most of that can be attributed to jumping out to big leads because of Manning, but if the Chargers can keep it close, Mathews should be a major factor.
Keenan Allen, on the other hand, has emerged as the best wide receiver in the 2013 rookie class. The Chargers have been looking for a number one receiving option for the past two seasons since Vincent Jackson left as a free agent, and Allen has stepped up to the challenge since being drafted in the third round out of Cal.
Going over 100 yards in three of his last four games, Allen should go over that total easily in this matchup, as the Chargers will have to air it out early and often to keep pace with the Denver offense. He has dropped a few balls, but his route running is fluid and he carries himself like a seasoned veteran. Look for Philip Rivers to find his new favorite target Allen in the end zone at least once on Sunday.
2. Peyton Manning will throw one touchdown pass to each of his three wide receivers and his tight end.
It is difficult to measure the precise quality of Manning's teammates because of his brilliance, but the biggest recipients of his passing prowess are clearly the ones catching the balls he throws. After signing Wes Welker as a free agent, the Broncos established arguably the best trio of wide receivers in the NFL.
With Demaryius Thomas and Eric Decker on the outside and Welker in the slot, the Denver passing game is difficult to slow down. They have performed as expected, but the biggest surprise for the Broncos has been tight end Julius Thomas.
A former basketball player in college, Thomas has followed the blueprint of other former college hoopers that have transitioned into unstoppable NFL tight ends. The list keeps growing, first it was Tony Gonzalez, then Antonio Gates, and more recently Jimmy Graham.
Thomas has eight touchdowns in as many games and with his size and athleticism, he is a reliable red zone target. The other three receivers are as well, and Peyton Manning can take advantage of defensive mismatches like few quarterbacks that have ever played.
On pace to shatter Tom Brady's single-season touchdown pass record, do not believe for one second that Manning is not conscious of that milestone.
3. The Chargers will find a way to win, with a final score of 41-38.
The odds are stacked against them, but the Chargers have a few advantages in this matchup that could play a big role. San Diego first-year coach Mike McCoy was Manning's offensive coordinator in Denver last season, and knows some of his tendencies. On the other sideline, the Broncos will be without their head coach John Fox for several weeks after he underwent a heart procedure.
That could work to their advantage from a motivational standpoint, but schematically, defensive coordinator Jack Del Rio will have to shift over to head coaching duties and the defensive playcalling could be affected.
Historically, the Chargers have performed well against Manning, upsetting him in the playoffs in both 2007 and 2008, as well as late in the regular season in 2005 to spoil his undefeated season. While those were different Charger teams with better defensive talent, Rivers was the quarterback and Manning has been known to have mental blocks in certain matchups.
Rivers is playing as well as any quarterback in the league not named Manning or Brees, and in a home game that is as close to must-win as a team can get in early November, expect Rivers to play extremely well. The new offense has emphasized shorter drop-backs and quicker releases to compensate for a injury-riddled offensive line, and that will be a key factor against a relentless Denver pass rush.
The Chargers will try to establish the run early, but Rivers is the glue of that offense, and he will make the clutch plays necessary to win, from converting crucial third downs to finishing drives in the red zone.
A seven point underdog, expect the San Diego Chargers to pull out a close game that could be another instant classic between these division rivals.