The Carolina Panthers also grabbed two major awards, with Ron Rivera winning AP NFL Coach of the Year and linebacker Luke Kuechly voted top defensive player.
Manning shattered the league record by throwing for 55 touchdowns. He also set a mark with 5,477 yards passing in leading the Denver Broncos to a 13-3 record, best in the AFC. They play Seattle on Sunday in the Super Bowl.
Broncos executive John Elway accepted the award on Manning's behalf.
"I can say I have never seen a better year played by a quarterback than Peyton Manning," Elway said. "To see what he did this year, it was truly amazing."
Manning received 33 votes from a nationwide panel of 50 media members who regularly cover the league. He also won the award in 2004 and was runner-up last year to Adrian Peterson.
This time, running back LeSean McCoy of Philadelphia was second with 10 votes, followed by Kansas City running back Jamaal Charles with four.
Rivera engineered the Panthers' turnaround from a 7-9 record to 12-4, the NFC South title and a first-round playoff bye. Kuechly keyed a defense that allowed 241 points, less than every team except NFC champion Seattle.
Green Bay running back Eddie Lacy and Jets defensive tackle Sheldon Richardson were the top rookies for 2013.
San Diego quarterback Philip Rivers took the Comeback Player of the Year award at the NFL Honors show.
Rivera's fine work in his third season in charge in Carolina brought him 21 1/2 votes. That outdistanced Kansas City's Andy Reid, who got 13 1/2 votes. In his first year with the Chiefs, Reid took them from 2-14 to 11-5 and an AFC wild-card berth.
"I do feel a lot of pride because it has been a long journey, but it also was a part of the process," Rivera said. "Just like us getting to where we are winning 12 games was part of the process. We started, the team was 2-14 before I got there and we went to 6-10 and then 7-9, and this year we broke through at 12-4. It was part of the process of growing and developing."
Rivera is the second Panthers coach to win the award. Dom Capers was AP Coach of the Year in 1996, Carolina's second season in the NFL.
Kuechly added top defensive player to his 2012 defensive rookie award. Carolina's All-Pro linebacker received 19 votes, ahead of Indianapolis All-Pro linebacker Robert Mathis, who earned 11 1/2.
Kuechly was credited with 96 tackles, four interceptions, two sacks, eight passes defensed, and was a presence from sideline to sideline on the NFL's No. 2 unit.
A second-round pick (61st overall) from Alabama, Lacy was a key performer in the Packers' offense, particularly when star quarterback Aaron Rodgers was sidelined for seven games. He rushed for 1,178 yards on 284 carries (4.1 average), with 11 touchdowns. He also had 35 receptions.
That was good enough for 35 votes.
"I'm comfortable where I am, and my teammates believe in me, and they make me feel comfortable, so I'm able to play the way I'm capable of playing," said Lacy, who beat out San Diego wide receiver Keenan Allen, who received 12 votes.
Richardson, the 13th overall pick in April's draft on a selection acquired when New York traded star cornerback Darrelle Revis to Tampa Bay, won a close race over Buffalo linebacker Kiko Alonso. Richardson received 23 votes; Alonso, a second-round choice (46th overall), got 19.
Often double-teamed as the season wore on, Richardson made 42 tackles and had 3 1/2 sacks. He clogged the running lanes so effectively that the Jets ranked third against the run this season.
"I'm surprised," Richardson said of beating Alonso and Arizona safety Tyrann Mathieu, who got two votes. "Kiko and Tyrann most definitely had outstanding rookie years and it was a toss-up to me. Kiko made a lot of tackles and Tyrann made a lot of plays down the field. Unfortunately he got hurt, but it was a tight race."
Richardson joked about the possibility of winning both awards he scored two touchdowns as a fullback in goal-line situations.
"Eddie Lacy beat me out there," Richardson said. "He had a few more touchdowns than I did."
Rivers led the Chargers to a wild-card playoff spot with four straight victories to close out the schedule, giving them a 9-7 record. He led the league with a 69.5 completion rate and threw for 32 TDs against 11 interceptions.
He received 13 votes in balloting so widespread that 12 players got votes. He was not at the awards show at Radio City Music Hall.
Chicago cornerback Charles Tillman won the Walter Payton Man of the Year award, and accepted the honor with tears in his eyes.
"As a Chicago Bear, this award has a special meaning to me," Tillman said.