The San Francisco 49ers fell to their first defeat of the NFL season with a 24-13 reverse at the hands of the Minnesota Vikings.
Christian Ponder threw two touchdown passes to Kyle Rudolph to hand Minnesota a 2-1 record this campaign.
The 49ers had started their NFC challenge with victories over Green Bay and Detroit, but found the Vikings too much to handle.
Chicago also boast a 2-1 record after they powered past the St Louis Rams 23-6.
The Bears were already in control when Major Wright returned an interception 45 yards for a touchdown in the fourth quarter.
Sam Bradford was sacked six times by the Bears defence.
The Cleveland Browns fell to a 3-0 record with a 24-14 loss against Buffalo.
Ryan Fitzpatrick threw three touchdown passes for the Bills, setting up CJ Spiller, TJ Graham and Stevie Johnson.
Both teams have 2-1 records following the result.
Blaine Gabbert was the hero for Jacksonville in a 22-17 win over Indianapolis.
Gabbert connected with Cecil Shorts III on an 80-yard touchdown pass with just 45 seconds remaining to steal some of the limelight from Jaguars team-mate Maurice Jones-Drew, who rushed for 177 yards.
Cincinnati have Andy Dalton to thank for their 38-31 win over Washington after he completed 19 of 27 passes for 328 yards and three touchdowns.
The Redskins had fought back from 24-7 down at the interval, but Dalton's display wrapped things up for the Bengals in the fourth quarter with Jermaine Gresham and Andrew Hawkins touching down.
Dan Bailey kicked three field goals to help the Dallas Cowboys see off Tampa Bay 16-10.
A 26-yard field goal from Rob Bironas in overtime saw Tennessee edge past Detroit 44-41, while Kansas City also needed an extra period of play to see off New Orleans 27-24.
Ryan Succop kicked six field goals for the Chiefs, including the decisive one from 31 yards in overtime.
The fixture between the New York Jets and Miami also went to overtime, with the Dolphins eventually succumbing 23-20.
It took a 33-yard field goal from Nick Folk with 6:04 left to separate the sides.
