The last time Manning encountered the Chargers was Nov. 28, 2010, when his team was destroyed in a 36-14 loss. During that game, Manning threw four interceptions, two of which were returned for touchdowns.
Manning's personal record against the Chargers is 1-5, but will he be able to defy his previous odds now that he's joined the Broncos?
The Broncos and the Chargers have always had a great rivalry, and this year is no different. Both teams are competing to become AFC West champions and for a playoff spot in their division.
Let's take a look at Monday's matchup.
Both AFC West teams have had a rough start to the season.
The Chargers faced the Atlanta Falcons in an upsetting 27-3 loss during Week 3, and the Broncos also lost to the Falcons with a final score of 27-21.
To make matters worse for Denver, the Broncos then had to face, and lost to, the Houston Texans the following week.
The Chargers are currently No. 1 in the AFC West, but this game can change that.
It's been difficult to tell how talented both of these teams really are. The Chargers have three wins, but the teams they beat were the Oakland Raiders, Kansas City Chiefs and Tennessee Titans, three of the worst teams in the NFL.
And the Broncos have only beaten Oakland and the Pittsburgh Steelers.
This matchup will decide which team outranks the other. It will also show how well each team can perform when it plays against a similarly matched opponent.
The San Diego Chargers and Denver Broncos offenses are very similar.
They are both successfully able to command the field in order to make plays happen.
So what does this mean?
Offensively, either team can take the lead in this Week 6 matchup. They will both perform effectively, which means the defenses will decide this game.
In Week 5, both defenses allowed their opponents to score 31 points on them. This week, both teams need to step up defensively if they want a chance for a victory.
If the Chargers allow the Broncos to make huge plays like they did for the New Orleans Saints, Peyton Manning will take full advantage and put big points on the board.
The same applies to the Broncos. Last week, the Denver defense allowed the New England Patriots to get 35 first downs, which broke their franchise record.
This game will depend heavily on the defensive side since both offenses will perform well. Manning's chance at redemption against the Chargers relies on his defense and whether or not it can shut down San Diego.