The win ends Kansas City's reign as the last unbeaten NFL team and drops them into a tie with Denver (9-1) the AFC West lead.
The Chiefs (9-1) failed to record a sack for the second straight week as Manning completed 24 of 40 passes to help the Broncos rack up 427 yards of offense. The Broncos defense got to Alex Smith three times.
Denver scored ten unanswered point to start the game with a 54-yard Matt Prater field goal and a nine-yard connection between Manning and Julius Thomas late in the first quarter.
Smith marched the Chiefs down the field to start the second quarter and hooked up with a Dwayne Bowe for a six-yard scoring strike to cut the lead to 10-7. Smith completed 21 of 45 passes for 230 yards and two scores. He also rushed five times for 52 yards.
Denver punched back with Monte Ball whose first touchdown of the night put Kansas City in a 17-7 hole with 9:05 left before halftime. Ryan Succop cut it back to a one-possession game with a 20-yard field goal late in the second frame.
Ball's ran in the lone score of the third quarter to go along with Prater's third field goal to grab a 27-10 lead on the Chiefs with 7:06 remaining.
Smith connect with Anthony Fasano on a 10-yard score with under five minutes to go, trimming the deficit to 27-17, but couldn't lead the offense any closer.
Jamaal Charles finished with 78 yards on 16 carries.