Manning, who will lead the Broncos against the Seattle Seahawks in the Super Bowl on Sunday, was the clear favourite in the MVP race after he set single season marks for touchdown passes (55) and yards (5,477).
Manning, who had neck surgery in 2011 and missed the entire season before being released by Indianapolis and signed by Denver in 2012, also won the award in 2009, 2008, 2004 and shared it with Steve McNair in 2003.
No one other than Manning had won MVP honours four-times and only quarterbacks Johnny Unitas, Brett Favre and running back Jim Brown have captured the award three occasions.
Manning was not on hand to accept the award at New York's Radio City Music Hall leaving that duty to his son Marshall and father Archie, a former New Orleans Saints quarterback, though he did send a pre-recorded message.
"This is a very special award," Manning said in the message.
"I am extremely honored to have it presented by Joe Montana and Aaron Rodgers.
"I am humbled by this recognition and grateful to my family, Pat Bowlen, John Elway, John Fox and the entire Denver Bronco organisation, and of course, my coaches and my teammates."
After 14 seasons with the Indianapolis Colts, not even Manning was certain how long it would take to recover from his surgery and adjust to a new team.
But after just two years in Denver, Manning has the Broncos back in the Super Bowl for the first time in 15 years.
With Manning at the controls of Denver's powerhouse offense, the Broncos scored a record 606 points, 161 ahead the next best team.
There is no disputing Manning's Hall of Fame credentials but with just one Super Bowl ring, where he ranks among the sport's best has been a subject of fierce debate.
When it comes to Super Bowl wins, Peyton is not even the best quarterback in the Manning family with younger brother Eli having guided the New York Giants to two titles.
The Broncos were tipped as Super Bowl favorites from the start of season and Manning has been under mounting pressure to prove that he can also get the job done when it counts most and turn his record-setting campaign into a Super Bowl title.
With a win over the Seahawks on Sunday, Manning would become the first quarterback to win the Super Bowl as starter for two different teams.
The fifth MVP award along with a second Super Bowl ring would cement Manning's credentials as one of the top two-or-three quarterbacks of all-time and certainly would not hurt the likeable quarterback's incredible popularity.
Already the NFL's most marketable player, Manning pulls in an estimated $12 million a year in endorsements, ranking 21st overall across all sports according to Forbes.
Other big winners were the Carolina Panthers, with Ron Rivera taking coach of the year honours after guiding his team back to the post-season while linebacker Luke Kuechly was voted defensive player of the year.
New York Jets defensive tackle Sheldon Richardson was voted defensive rookie of year while Green Bay Packers running back Eddie Lacy grabbed offensive rookie honours.
San Diego Chargers quarterback Philip Rivers was named comeback player of the year while Chicago Bears defensive back Charles Tillman accepted the Walter Payton man of the year award.
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