Andrew Luck passed for three touchdowns and ran for another as the Indianapolis Colts beat their former quarterback Peyton Manning and the Denver Broncos 39-33, while elsewhere the Pittsburgh Steelers got a win over the Super Bowl champion Baltimore Ravens and New England fell to the New York Jets in overtime.
The Broncos (6-1) saw their 17-game regular-season winning streak snapped, leaving the Kansas City Chiefs (7-0) as the NFL's only unbeaten team.
Manning won four MVP awards and a Super Bowl title in 13 years with the Colts before they allowed him to become a free agent, clearing the way for Indianapolis to select Luck with the first pick of the 2012 draft.
The Colts honored Manning before the game with a video presentation and crowd applause before Manning passed for 386 yards and three touchdowns, completing 29 of 39 passes in his first game against them. He was intercepted once.
"There's no question that was emotional during that tribute," Manning said. "I felt probably a little tired coming into this week. I'm kind of, in some ways, somewhat
relieved this game is over."
Denver's Eric Decker had eight catches for 150 yards and a score.
Luck went 21-for-38 for 228 yards and ran four times for 29 yards for the Colts (5-2).
"I have never looked at it as the guy that replaced Peyton. I just looked at it as a chance to play football for a great team," Luck said.
In Kansas City, Alex Smith threw for 240 yards while rushing for a touchdown, and the stingy Chiefs defense helped keep them unbeaten with a 17-16 victory over the Houston Texans.
The Chiefs held an injury-plagued Houston offense to a pair of Randy Bullock field goals while sacking back up quarterback Case Keenum five times over the final two quarters to make a 14-10 halftime lead stand up.
The surprising Chiefs improved to 7-0 on the season.
Smith finished an efficient 23-of-34 with an interception, while Jamaal Charles rushed for 86 yards and a touchdown on 21 carries.
"It feels real good," Charles said of being 7-0. "I'm just blessed that we win games and that we continue to win and that we have a defense that fights and saves the offense."
In East Rutherford, New Jersey, Nick Folk made the most of a second chance at a game-winning field goal, drilling a 42-yarder with just over five minutes left in overtime to give the New York Jets a 30-27 win over the New England.
Folk at first pulled a 56-yard try wide to the left, but was given a reprieve when Patriots were called for unsportsmanlike conduct for pushing one of their players into a Jets' blocker.
The penalty moved the ball inside the New England 25, and Folk made good on the second attempt to complete New York's comeback from an 11-point halftime deficit.
Carpenter makes good
The other AFC East showdown was also a thriller, with the Buffalo Bills pulling off a 23-21 road win over the Miami Dolphins as Dan Carpenter kicked the winning field goal from 31 yards with 33 seconds left.
The Dolphins, who failed on a 'Hail Mary' attempt as time expired, fell to 3-3 for the season, while the Bills moved to 3-4 in what has suddenly become a tightly-bunched division.
The San Francisco 49ers and Cincinnati Bengals both improved to 5-2.
The AFC North Division leading Bengals beat the Detroit Lions 27-24 on Mike Nugent's 54-yard field goal as time expired and the 49ers, chasing the Seattle Seahawks in the NFC West, topped the Tennessee Titans 31-17.
The struggles continued for reigning Super Bowl champions Baltimore (3-4), who fell to the Pittsburgh Steelers 19-16 on a game-ending field goal, while the Dallas Cowboys (4-3) cemented their NFC East lead with a 17-3 victory over Philadelphia, whose quarterback Nick Foles suffered a head injury.
Chicago quarterback Jay Cutler was also injured, experiencing an apparent groin problem in a 45-41 loss to Washington.
Cam Newton passed for 204 yards and a touchdown to lead the Carolina Panthers to a 30-15 victory over the St Louis Rams at Bank of America Stadium.
Before leaving the game with a bad leg injury, Rams quarterback Sam Bradford completed 21 of his 30 pass attempts for 255 yards and a touchdown pass to Zac Stacy.