The Atlanta Falcons' unbeaten run was ended by the New Orleans Saints on Sunday with a 31-27 loss at the Superdome, while defending Super Bowl champions the New York Giants suffered a shock 31-13 loss at the Cincinnati Bengals.
The Buffalo Bills came close to producing another upset against New England but quarterback Ryan Fitzpatrick threw a late interception as the Patriots hung on for a 37-31 win.
There was a rarity in San Francisco where the 49ers and Rams tied 24-24 after overtime - the first tie in almost four years.
Falcons quarterback Matt Ryan passed for three touchdowns and 411 yards but ended on the losing team for the first time this season as the Saints (4-5) showed they may still have a slight sniff at a place in the playoffs.
Tight end Jimmy Graham had a stellar day for New Orleans with two touchdowns and 146 yards on seven receptions while quarterback Drew Brees threw for three touchdowns and 298 yards.
The Falcons were foiled at the end by two strong stands from the oft-criticized Saints' defense with the game saved by brilliant defensive work from cornerback Jabari Greer.
Atlanta had fourth and goal from the Saints' two-yard line with 1:46 on the clock when Ryan passed the ball towards receiver Roddy White in the middle of the end zone but Greer threw himself at the ball and batted it away.
While the result will change little in the NFC South standings, the game showed the Saints have fully recovered from their 0-4 start and the Falcons (8-1) may have some work left to do if they are to be a real threat in the playoffs.
The New York Giants (6-4) suffered their second successive loss, and their defeat to the unheralded Bengals, who had lost their last four games, will cause much more concern than last week's defeat to the Pittsburgh Steelers.
Coach Tom Coughlin will be glad for the upcoming bye-week to fix his team's troubles after a game in which New York quarterback Eli Manning threw two interceptions which led to Bengals touchdowns.
Bengals quarterback Andy Dalton had four touchdowns passes for the first time in his NFL career, starting off with a 56- yard connection to the impressive A.J. Green and ending with a 10-yard pass to Mohamed Sanu.
The Giants risked going without a touchdown until Andre Brown scored from two yards in the fourth quarter.
Questions will remain about the New England Patriots' defense despite their narrow victory over AFC East rivals Buffalo although Devin McCourty's quick-witted interception at the end saved the game.
Stevan Ridley put up 98 rushing yards for the Patriots with Tom Brady throwing for 237 yards and two touchdowns but their defense was exposed by Bills running back Fred Jackson who had two touchdowns and 80 rushing yards.
The Bills had 481 yards total offense and enjoyed 6.8 yards per offensive play - numbers that will concern Patriots head coach Bill Belichick despite his team leading the AFC East with a 6-3 record.
A 33-yard field goal from 49ers kicker David Akers pushed their game with the Rams into overtime but neither side were able to score in the extra period.
Akers missed from 41 yards and then Greg Zuerlein looked to have scored with a 53 -yarder for the Rams but the officials called 'delay of the game' and he missed the re-taken kick from 58 yards.
It was just the 18th tie since the NFL introduced regular season overtime in 1974.
The Baltimore Ravens move to 7-2 after crushing the Oakland Raiders 55-20 with Joe Flacco throwing for three touchdowns and 341 yards.
The Ravens had four receivers who put up more than 50 yards in the one-sided game.
Peyton Manning and the Denver Broncos also enjoyed a relatively comfortable win with a 36-14 victory at the Carolina Panthers.
Manning threw for 301 yards and a touchdown to move into a second place tie with Dan Marino on the NFL all-time list with 420 passing TDs while his opposite number Cam Newton was sacked seven times and threw two interceptions.
The Minnesota Vikings' (6-4) impressive season continued with Adrian Peterson rushing for 171 yards in a 34-24 win over the Detroit Lions. Peterson set up the victory with a 61-yard touchdown run in the fourth quarter.
Philadelphia Eagles quarterback Michael Vick suffered a concussion and was taken out of the game against the Dallas Cowboys early in the second quarter.
The Cowboys went on to a 38-23 win and in an unusual fourth quarter they scored touchdowns on a punt return, interception return and fumble recovery.
The Seattle Seahawks move to 6-4 after a comfortable 28-7 win over the fading New York Jets who fall to 3-6.
The Tampa Bay Buccaneers enjoyed a third successive win with a 34-24 victory over the San Diego Chargers. Leonard Johnson returned an interception 83 yards in the fourth quarter for the decisive score.
(Reporting By Simon Evans, editing by Gene Cherry)