After a first-round bye the top-seeded Broncos (13-3) join the playoff mix led by future Hall of Fame quarterback Manning, who is fresh off setting single-season records for passing yards (5,477) and touchdowns (55).
Denver's explosive offense scored a record 606 points in 16 regular season games, 161 points ahead the next closest pursuer.
"All the records and all the stats go out the window," said Denver head coach John Fox. "It's a whole new season.
"The key is playing the best football during the playoffs. It's a single-elimination tournament, so you can't have a bad day.
"You have to be on your game from beginning to end."
Both the Chargers and host Broncos will enter new territory on Sunday, the two teams having faced one another 108 times but never in the post-season.
But certainly San Diego head coach Mike McCoy is aware of the challenge his team faces in slowing down Manning and the Broncos high-octane attack having worked as Denver's offensive coordinator for four seasons before joining the Chargers.
Manning will operate with an arsenal of weapons that allow him to attack San Diego's 29th-ranked defense from every angle. During the regular season only Minnesota, Philadelphia and Dallas allowed more yards per game.
Knowshon Moreno, who rushed for over 1,000 yards for the first time in his career will do most of the work on the ground. But it is through the air that Denver inflict most of their damage with Manning targeting Wes Welker, Eric Decker and Demaryius Thomas, who had three touchdowns in the Broncos 28-20 win over the Chargers last November.
"It's another game to us," McCoy said during a conference call. "When you look at it, we're going to play the same.
"We're going to do what we do, the coaches are going to put their best game plan together, and go out and have the players execute it."
After their playoff hopes seemed dead and buried entering the final month of the regular season, the red-hot Chargers roll into the Mile High city riding the momentum of a five-game winning streak.
While Rivers did not come close to matching Manning's regular season, the 10-year veteran still enjoyed one of his best campaigns, passing for 4,478 yards, 32 touchdowns against 11 interceptions while guiding the Chargers back to the playoffs for the first time in four years.
Rivers also has an impressive arsenal of offensive weapons to draw upon, including veteran tight end Antonio Gates, rookie wide receiver sensation Keenan Allen, sure-handed Eddie Royal and diminutive running back Danny Woodhead.
"It's not me versus him (Manning) by any means and this is a new team and he's in a new place, new deal," said Rivers.
"I know history there's certain records and things as far as how you stack up against certain opponents and you mention since I've been here what our record has been in Denver, but I really think every game stands alone and all that stuff throws out the window, especially in a playoff game."