One mistake by Dallas quarterback Tony Romo cost the Cowboys dear against Denver on Sunday as Peyton Manning led the Broncos to their fifth straight win, while Andrew Luck sparked a Colts comeback that spoiled Seattle's spotless record.
On a day that featured five teams putting perfect records on the line, New Orleans (5-0) and Kansas City (5-0) kept their runs alive while New England (4-1) fell to Cincinnati with Tom Brady's streak of 52 consecutive games with a touchdown pass came to an end.
Dueling Denver and Dallas (2-3) quarterbacks Manning and Romo combined for 920 yards passing and nine touchdown throws in an explosive encounter in Texas, but it was Romo's interception with under three minutes left that sealed the outcome.
With the score tied 48-48, Romo threw an interception deep in his own territory and Matt Prater kicked a last-second 28-yard field goal to give Denver the win.
In Indianapolis, quarterback Luck (below) engineered a fightback that led the Colts to a 34-28 win over the Seahawks.
"Guys kept fighting," Luck told reporters. "It's been that way since I've been here."
With his team trailing most of the game, and facing a 28-23 deficit entering the final quarter, the former first overall 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 Seattle signal caller Russell Wilson finished 15-of-31 for 210 yards with two touchdowns and an interception.
In Cincinnati, the Patriots fell 13-6 to the Bengals (3-2) with Brady failing to find the endzone with a touchdown pass for the first time in 52 games.
There were no such problems for Saints quarterback Drew Brees, who completed 29 of 35 passes for 288 yards and two touchdowns in leading New Orleans to a 26-18 victory over the Bears (3-2) in Chicago.
Jimmy Graham extended his torrid start by catching 10 passes for 135 yards in his fourth consecutive 100-yard game, matching an NFL record for a tight end.
In Tennessee, Kansas City, one season removed from finishing last in the NFL but rejuvenated under a new head coach and quarterback, got a one-yard touchdown run from Jamaal Charles (below) to pull ahead of the Titans (3-2) with about six minutes to play en route to a 26-17 win.
Bolstered by the off season 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.
"I'm speechless right now," Charles said. "This team is very blessed to be 5-0 right now. Nobody expected us to be 5-0."
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.