Matt Bryant kicked a 55-yard field goal with one second to play to give the unbeaten Falcons (6-0) a 23-20 win over the visiting Oakland Raiders (1-4).
Falcons quarterback Matt Ryan, who threw three interceptions in the first half, saved his best for last, engineering the game-winning drive after Oakland tied the score with 40 seconds left in regulation.
The New York Giants crushed the San Francisco 49ers in an ominous sign of their intentions to defend their Super Bowl title.
The Giants (4-2) made light work of the 49ers (4-2), the team that beat in last year's NFC Conference final, to win 26-3, while last season's AFC champions, the New England Patriots, suffered a surprise loss to the Seattle Seahawks.
The Cleveland Browns finally registered their first victory of the season.
The Houston Texans suffered their first defeat of the season, losing 42-24 to the resurgent Green Bay Packers, and the Baltimore Ravens survived a nail-biter with the Dallas Cowboys for their fourth successive win.
There were also wins for the New York Jets, Detroit Lions, Tampa Bay Buccaneers, Miami Dolphins, Buffalo Bills and the Washington Redskins.
The Giants gave 49ers quarterback Alex Smith a torrid time, sacking him six times and making three interceptions while New York signal-caller Eli Manning threw for 193 yards and a touchdown, to Victor Cruz.
"Coming in to this game, we knew it was a great challenge to see where we stand," Manning said in a televised interview from Candlestick Park.
"That's what we did at the end of last season... we're getting back into that rhythm of playing smart."
Seattle (4-2) stunned the Patriots (3-3) with a late touchdown when Russell Wilson found Sidney Rice for a 46-yard touchdown pass down the middle, overturning a 13-point deficit in the last 10 minutes to win 24-23.
The Cleveland Browns (1-5) piled on 27 points in the second half to defeat the Cincinnati Bengals 34-24 and snap an 11-game losing streak dating back to November of last season.
The Bengals fell to 3-3, two wins behind a 5-1 Ravens team that tightened their grip on top spot in the AFC North division after beating the Cowboys 31-29 in a thriller.
Packers quarterback Aaron Rodgers completed 24 of 37 passes for 338 yards and a single game career-high six touchdowns to improve Green Bay's record to 3-3 as the Texans slipped to 5-1 after making a perfect start to the season.
Dallas had a chance to force overtime after receiver Dez Bryant scored a touchdown with 32 seconds left but he then failed to catch the two-point conversion pass.
The Cowboys (2-3) gave themselves another chance to pinch victory when they recovered the ensuing onside kick to set up a 51-yard field goal attempt that Dan Bailey just missed.
The Jets thrashed the Indianapolis Colts 35-9 to snap a two-game losing streak as running back Shonn Greene rushed for a career-best 161 yards and three touchdowns.
The Detroit Lions overcame a 10-point deficit in the last quarter to beat the Philadelphia Eagles 26-23 in overtime and end a four-game losing streak.
Jason Hanson kicked the winning field goal from 45 yards in overtime as the Lions improved to 2-3 and the Eagles, who got 311 passing yards two touchdowns and two interceptions from quarterback Michael Vick, fell to 3-3.
Ryan Tannehill threw a pair of touchdown passes as Miami (3-3) held on to beat the visiting St. Louis Rams 17-14.
St. Louis (3-3) had an opportunity to tie the game as time expired but rookie kicker Greg Zuerlein sent a 66-yard field goal attempt wide.
Tampa Bay quarterback Josh Freeman threw for 328 yards and three touchdowns as the Buccaneers (2-3) posted their first win in four games with a 38-10 victory over the Kansas City Chiefs (1-5).
Rian Lindell kicked a 25-yard field goal in overtime to give Buffalo (3-3) a 19-16 win over the Arizona Cardinals (4-2) to join the Patriots, Jets and Dolphins a four-way tie in the AFC East.
Rookie quarterback Robert Griffin III ran in two touchdowns, including one from 76 yards, to give the Redskins (3-3) a 38-26 win over the Minnesota Vikings (4-2).
