© Getty Images
As well as falling behind, Kansas City were dealt another blow in the first quarter when Jamaal Charles picked up an injury, ruling him out for the remainder of the game.
Rookie kicker Cairo Santos reduced the home side's arrears with a field goal after Alex Smith had failed to find Junior Hemmings and Dwayne Bowe, although Knile Davis did manage a short rush for the Chiefs' opening touchdown.
Manning came back onto the field and spread the ball around his receivers, with touchdowns for Jacob Tamme and Demaryius Thomas before the end of the second quarter.
The Chiefs made a patient start to the second half, spending 10 minutes on the opening drive of the game, but they were unable to find the endzone, while Santos sliced his field-goal attempt wide.
The visitors kept pressing, though, with Smith handing the ball off to Davis for the running back's second score of the game, leaving the Chiefs less than a touchdown behind in the final quarter.
The visitors were closing in on the endzone again in the final moments, but Davis could not break through the Broncos defense, while Bowe was brought down short by Terrance Knighton on the final play of the game.
The result leaves the Broncos at the top of the AFC West, with the only unbeaten record in the division.