Their lead was nearly furthered as Flacco looked to seal another touchdown pass, but this time Chris Harris intercepted when Brandon Stokley looked likely to put John Harbaugh's men in front.
Ray Rice went over in the second period, but another quality throw from Manning saw Julius Thomas dart down the middle to score, and Matt Prater kicked the extra point.
Justin Tucker's boot had the Ravens in front before the interval, but the hosts were soon in front as Andre Caldwell collected a pass from Manning to score a touchdown.
Manning then caught Wes Welker out with a simple pass as the Broncos staged a valiant fightback.
The Broncos continued to display their fighting characteristics as Manning located Decker with a beauty in the endzone, but he dropped the ball. He then found Welker again with the next play, for another strike.
Eventually, Manning did get his sixth touchdown of the night, with Demaryius Thomas catching the ball in the endzone.
Flacco found Marlon Brown for a score before Manning and Demaryius Thomas combined to for his record-equalling seventh touchdown to secure the Broncos' first victory of the season, taking the score to 49-27.
The defeat was Baltimore's first on the opening day since the 2007 season and they conceded the highest number of points in one game in the history of their franchise.