The Miami Dolphins overcame the New England Patriots for the first time in eight attempts with a 24-20 victory in the AFC East.
Ryan Tannehill threw for three touchdowns and 312 yards for the Dolphins as Patriots counterpart Tom Brady saw his final pass intercepted as the visitors attempted to seal a comeback.
The loss is just the fourth of the season for the division leading Patriots who are now 10-4 for the season while the Dolphins move to 8-6.
The Seattle Seahawks cruised to a 23-0 win over the New York Giants to claim their sixth road win of the season.
Russell Wilson ran for 50 yards and threw for 206 and a touchdown as the Seahawks held their hosts to just 181 yards to move to 12-2 for the campaign.
The Minnesota Vikings ended the Philadelphia Eagles' five-game winning streak with a 48-30 victory.
Matt Cassel passed for 382 yards and two touchdowns and ran for another score as the injury-hit Vikings moved to 4-9-1 on the season.
Jay Cutler returned from his injury lay-off to throw three touchdown passes as the Chicago Bears beat the Cleveland Browns 38-31.
The quarterback had missed the last four games with an ankle problem but showed no signs of rust as he threw for 265 yards to help the Bears move to 8-6.
The AFC South champion Indianapolis Colts claimed their ninth win of the season as they brushed past the Houston Texans 25-3.
The game was effectively over at half-time with the Colts leading 20-3 as Andrew Luck threw for 180 yards and two touchdowns.
EJ Manuel threw two touchdown passes as the Buffalo Bills claimed a 27-20 victory over the Jacksonville Jaguars while the San Francisco 49ers sealed a 33-14 win over the Tampa Bay Buccaneers.
A fourth-quarter touchdown was not enough for the Washington Redskins as they fell to a narrow 27-26 defeat to the Atlanta Falcons.
Cam Newton threw for 273 yards and a touchdown and Captain Munnerlyn had two sacks and returned an interception for a score as the Carolina Panthers defeated the New York Jets 30-20.
Jamaal Charles tied a franchise record with five touchdowns in a game and Alex Smith threw five TD passes as the Kansas City Chiefs beat the Oakland Raiders 56-31 to clinch at least a wild-card spot.
Matt Flynn threw four touchdown passes in the second half and Eddie Lacy had the winning score on a one-yard plunge for the Green Bay Packers who matched the biggest comeback in franchise history, rallying from 23 points down at half-time to beat the Dallas Cowboys 37-36.
The St Louis Rams beat the New Orleans Saints 27-16 and the Arizona Cardinals needed overtime to defeat the Tennessee Titans 37-34.
Antonio Brown caught a touchdown pass and returned a punt for a score in a 64-second span in the first quarter as the Pittsburgh Steelers beat the Cincinnati Bengals 30-20.
Shaun Suisham added three field goals for the Steelers (6-8), who built a 24-point lead and hardly looked like a team playing out the string.
Ben Roethlisberger completed 20 of 25 passes for 191 yards with a touchdown and an interception. Le'Veon Bell added 117 yards of total offense.