The Broncos were trailing 21-14 at halftime but Decker and Manning then hooked up for three straight scoring strikes to put Denver ahead.
The Chiefs got to within seven points after Jamal Charles' 1-yard touchdown with 6:32 remaining, but couldn't get any closer as their final drive came up short.
Manning completed 22-of-35 passes for 403 yards and shook off a pair of interceptions for the Broncos (10-2), who bested AFC West rival Kansas City (9-3) for the second time in three weeks.
Manning set a Broncos record by reaching 41 TDs for the season. Decker finished with eight catches for 174 yards, establishing a new club mark for most scoring grabs in a single game.
Alex Smith made good on 26-of-42 passes for 293 yards and two TDs for the Chiefs.
Knile Davis pulled off the longest play in Kansas City history with a 108-yard kickoff return for a touchdown.
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