The Broncos trailed by three at halftime, but then rode the momentum of a key play early in the third quarter to overwhelm the defending Super Bowl champion Ravens.
Manning completed 27-of-42 passes for 462 yards and became the sixth player in NFL history to throw for seven touchdowns in a game. Chicago's Sid Luckman was the first to do so in 1943 and the most recent addition to the list had been Minnesota's Joe Kapp in 1969.
The outstanding performance was finished off when Manning hit Demaryius Thomas with a 78-yard scoring pass with 5:29 to play. Thomas, Wes Welker and Julius Thomas all caught two touchdown throws with Demaryius Thomas accounting for 151 yards and Julius Thomas for 110.
Despite all that, Denver trailed 17-14 at halftime and appeared likely to surrender possession early in the third quarter when a third-down pass from Manning-to-Welker that was ruled complete was shown by replays to have hit the ground.
There was no replay challenge forthcoming, however, from Baltimore Coach John Harbaugh. Instead of being forced to punt, Denver quickly scored and dominated the rest of the way.
Three plays after the lack of a challenge, Manning hit Andre Caldwell for a 28-yard touchdown that put the Broncos in front 21-17.
Denver blocked a Baltimore punt at the end of the Ravens' next possession, leading to a 5-yard touchdown throw from Manning to Welker. Manning finished off a 21-point third quarter with a 2-yard scoring toss to Welker and then found Demaryius Thomas with a 26-yarder just 14 seconds into the final period.
Manning also threw for two touchdowns in the first half, both of those going to tight end Julius Thomas for 24 and 23 yards.
Manning has 442 touchdown passes in his career, leaving him 56 away from catching Brett Favre for the No. 1 spot on the all-time list.
Welker caught nine passes for 67 yards in his debut with the Broncos. He signed as a free agent with Denver this year after playing six seasons with New England.
Baltimore's Joe Flacco went 34-of-62 for 362 yards with two touchdowns and two interceptions.
The 104 passes thrown in the game tied for the third most in league history. The all-time record for one game is 112 set by New England and Minnesota in an overtime contest played 13 years ago.