Denver scored 15 points in the fourth quarter and now leads the AFC West.
The game was played at Empower Field at Mile High in Denver on Sunday.
Will Lutz kicked a field goal for a 3-0 lead. Mahomes answered with an 11-yard touchdown to Rashee Rice.
Mahomes hit rookie Emmett Johnson for a 73-yard score. Nix found Jaylen Waddle on fourth down.
Mahomes led an 11-play drive and found Noah Gray for a 4-yard touchdown. Chiefs led 24-13.
Nix led an 80-yard drive and threw a 2-yard touchdown to Nate Adkins on fourth down. Waddle caught the two-point conversion.
After an Alex Singleton sack, Harrison Butker missed a 54-yard field goal. Denver got the ball back.
Nix found Jonah Coleman for 51 yards. On the next play, Coleman ran it in from the 5. Denver led 28-24.
The Chiefs reached the 1-yard line, but a false start pushed them back. Malcolm Roach sacked Mahomes to end it.
It was Kansas City's second straight loss. The Broncos moved to 6-2 and first place in the AFC West.
The win was coach Sean Payton's 200th career win. Denver entered as 1.5-point underdogs.
Kansas City hosts the New York Jets next Sunday. Denver travels to face the Carolina Panthers.
Get the full breakdown, key numbers, and what happens next.
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