Tom Brady was intercepted twice as the Tampa Bay Buccaneers suffered a shock 29-19 defeat at the Washington Football Team.
The reigning Super Bowl champions were coming off a bye week looking to atone for their defeat against New Orleans two weeks ago.
But they were stunned by a team without a win in the last month on a difficult afternoon for seven-time Super Bowl winner Brady, who threw two picks in the first quarter.
Brady threw second-half touchdowns to Cameron Brate and Mike Evans, but Washington produced an impressive fourth-quarter drive that ended with Antonio Gibson’s second rushing score of the game to put the result to bed.
Brady's former team the New England Patriots extended their winning run to four games with a stunning 45-7 thrashing of the Cleveland Browns.
Mac Jones, the Patriots quarterback, threw three touchdowns while fellow rookie Rhamondre Stevenson ran in two scores and Jakobi Meyers caught the first touchdown of his career.
Cleveland, who went into the game without top running backs Nick Chubb and Kareem Hunt, saw quarterback Baker Mayfield exit the game in the third quarter with a knee injury.
Cam Newton had a strong return to the Carolina Panthers, his first touch of the ball seeing him into the endzone and his second a pass for another score in a 34-10 win over the Arizona Cardinals.
Kirk Cousins threw two touchdown passes as the Minnesota Vikings beat the Los Angeles Chargers 27-20 and the Philadelphia Eagles breezed past the Denver Broncos 30-13.
The Buffalo Bills maintained their slim advantage over New England in the AFC East by swatting aside the New York Jets 45-17.
Buffalo responded to their embarrassing loss to the Jacksonville Jaguars last week in style, intercepting Jets quarterback Mike White four times while Josh Allen threw for 366 yards and two touchdowns for the Bills.
The Dallas Cowboys were another team to comprehensively bounce back from a defeat as they hammered the Atlanta Falcons 43-3.
Dak Prescott threw two touchdowns to CeeDee Lamb and rushed in for another, while running back Ezekiel Elliott also crossed the goal-line twice, ending any concerns the Cowboys had been figured out in their comprehensive loss to the Denver Broncos last Sunday.
Detroit's Kicker Ryan Santoso missed a potential game-winning field goal in overtime as the Lions' winless run to start the season continued with a rare 16-16 tie with the Pittsburgh Steelers.
The Tennessee Titans still have the best record in the AFC thanks to a battling 23-21 triumph over the New Orleans Saints.
Titans kicker Randy Bullock kicked 11 points while quarterback Ryan Tannehill threw one touchdown and rushed in for another, before the defence held off a surging Saints in the fourth quarter to improve their record to 8-2.
Elsewhere, the Indianapolis Colts improved to 5-5 with a 23-17 victory over the Jacksonville Jaguars, Russell Wilson threw two interceptions as the Seattle Seahawks were blanked by the Green Bay Packers 17-0 and the Kansas City Chiefs won against the Las Vegas Raiders 41-14.
