Manning threw two touchdown passes to lead Denver over visiting San Diego 24-17 while Colin Kaepernick ran for one touchdown and threw for another to lift the 49ers over host Carolina 23-10.
Denver will host New England and San Francisco will visit Seattle in next Sunday's playoff semi-finals with those winners to meet in Super Bowl 48 on February 2 at suburban New York.
Manning, who set new NFL pass yardage and touchdown toss records this season leading the top-scoring offensive unit in league history, will have a showdown against New England rival Tom Brady, whose records he broke, in a battle of star quarterbacks for the American Conference crown.
"It's the Broncos versus the Patriots," Manning said. "Tom and I have played against each other a lot but when you get to the conference championship it's about two good teams getting there."
The Patriots defeated Denver 34-31 in overtime in a regular-season matchup November 25 at New England. The Broncos led 24-0 at half-time before three-time Super Bowl winner Brady produced the greatest comeback of his NFL career.
Kaepernick, meanwhile, completed 15-of-28 passes for 196 yards and ran seven times for 15 yards as the 49ers shook off a slow start and avenged a 10-9 regular-season home loss to the Panthers last November.
San Francisco, who lost last year's Super Bowl to Baltimore, split two games with the Seahawks this season, losing 29-3 at Seattle in September but winning 19-17 at home last month.
Jim Harbaugh, the 49ers' coach, became the first coach in the Super Bowl era to reach the conference finals in each of his first three years guiding a team.
New England defeated Indianapolis 43-22 and Seattle downed New Orleans 23-15 in playoff matchups Saturday.
Manning flipped a 2-yard touchdown pass to Demaryius Thomas and a 3-yard touchdown pass to Wes Welker and Matt Prater added a 45-yard field goal to put Denver ahead 17-0 entering the fourth quarter.
San Diego's Philip Rivers sandwiched two 16-yard touchdown passes to rookie Keenan Allen around a 3-yard touchdown run for Denver's Knowshon Moreno in the fourth quarter.
The Chargers pulled within the final margin on Nick Novak's 30-yard field goal with 3:53 to play, but Manning connected with Julius Thomas on two third-down conversion passes that allowed the Broncos to run out the clock on San Diego's upset bid.
At Charlotte, San Francisco took a 6-0 lead on Phil Dawson field goals of 33 and 49 yards in the first quarter.
Carolina answered on Cam Newton's 31-yard touchdown pass to Steve Smith and the Panthers stretched their lead to 10-6 on Graham Gano's 24-yard field goal.
The 49ers responded with a 12-play, 80-yard march capped by Kaepernick's 1-yard touchdown toss to Vernon Davis, which counted only after a video review overuled him being called out of bounds.
That gave the 49ers a 13-10 half-time lead and they stretched it to 20-10 just 6:07 into the third quarter on a 4-yard Kaepernick touchdown run.
Dawson added a 34-yard field goal with 7:41 remaining for the final victory margin.