Andrew Luck outdueled Russell Wilson in a battle of second-year quarterbacks as the Indianapolis Colts dealt the Seattle Seahawks their first loss of the season on Sunday while New Orleans and Kansas City remained undefeated.
On a day that featured five teams putting perfect records on the line, the previously unbeaten New England Patriots (4-1) fell 13-6 to the host Cincinnati Bengals (3-2) as Tom Brady's streak of 52 consecutive games with a touchdown pass ended.
Peyton Manning and the Denver Broncos (4-0), looking to join New Orleans (5-0) and Kansas City (5-0) atop the standings, were among the late afternoon slate of games and will look to extend their perfect start at the Dallas Cowboys (2-2).
In Indianapolis, Luck sparked a comeback that allowed the Colts (4-1) to prevail over Seattle (4-1) in a 34-28 shootout.
With his team trailing most of the game and facing a 28-23 deficit entering the final quarter, the former first overall draft pick led Indianapolis on an 84-yard drive that put the Colts up for good when Donald Brown scored on a three-yard run.
Luck completed 16 of 29 passes for 229 yards and two touchdowns while Wilson finished 15-of-31 for 210 yards with two touchdowns and an interception.
In Chicago, Drew Brees completed 29 of 35 passes for 288 yards and two touchdowns in leading the Saints (5-0) to a 26-18 victory over the host Chicago Bears (3-2) and the best record in the NFC.
New Orleans tight end Jimmy Graham extended his torrid start to the NFL campaign by catching 10 passes for 135 yards in his fourth consecutive 100-yard game - matching an NFL record for a tight end.
The Chiefs, one season removed from finishing last in the NFL but rejuvenated with a new head coach and quarterback, got a one-yard touchdown run from Jamaal Charles to pull ahead of the Tennessee Titans (3-2) with about six minutes to play en route to a 26-17 win.
Bolstered by the offseason acquisitions of quarterback Alex Smith and head coach Andy Reid, the Chiefs are off to their best start since opening the 2003 campaign with nine consecutive wins and are challenging Denver for top spot in the AFC West.
Philadelphia Eagles (2-3) quarterback Nick Foles took over for an injured Michael Vick and propelled his team to a 36-21 win that dropped the host New York Giants to 0-5.
Vick left the game with a hamstring injury in the second quarter, but Foles was poised in a two-touchdown performance that could create a quarterback controversy in Philadelphia.
The spiraling Giants lost running back David Wilson to a neck injury in the first quarter and their disastrous season continued.