Josh Allen passed for 315 yards and added 59 yards rushing as the Buffalo Bills' top-ranked defence stuffed Patrick Mahomes and the Kansas City Chiefs 38-20 at a soggy Arrowhead Stadium.
A line of thunderstorms prompted a 62-minute delay at half-time and rain persisted in the second half.
The victory avenged the Bills' 38-24 loss to the Chiefs in last year's AFC Championship game and kept Buffalo (4-1) in charge of the AFC East.
Kansas City (2-3) fell to last place in the AFC West after their second straight loss at home.
STOP IT, JOSH. #BillsMafia
— NFL (@NFL) October 11, 2021
📺: #BUFvsKC on NBC
📱: https://t.co/6zBjGnL9LY pic.twitter.com/OTRsDYY7ML
The Arizona Cardinals spoiled rookie Trey Lance's NFL starting debut with a first-quarter interception and four fourth-down stops to pave the way for a 17-10 victory over the visiting San Francisco 49ers.
Lance got the better of rival Kyler Murray in total yards, but the Arizona star threw a nine-yard touchdown pass to DeAndre Hopkins with just over five minutes remaining to allow the Cardinals (5-0) to retain their status as the league's only unbeaten team.
Austin Ekeler scored three fourth-quarter touchdowns and the Los Angeles Chargers overcame a 14-point deficit in the second half to defeat the Cleveland Browns 47-42 in Inglewood.
Justin Herbert finished with a career-high 398 passing yards and completed 26 of 43 passes for the Chargers (4-1). Herbert threw four touchdown passes and no interceptions. He also ran for a score.
Every touchdown from NFL RedZone in Week 5! 🔥 pic.twitter.com/ssJkzn4Zwu
— NFL (@NFL) October 11, 2021
Dak Prescott threw for 302 yards and three touchdowns as the Dallas Cowboys overcame a slew of first-half mistakes to knock off shorthanded New York Giants 44-20 in Arlington.
Prescott completed 22 of 32 passes, making up for a sloppy first half in which he tossed an interception and lost a fumble. Ezekiel Elliott added 110 yards and a late touchdown on 21 rushes as Dallas (4-1) assumed a two-game lead in the NFC East.
New York hung with the Cowboys for just over a half before its injury-riddled offence simply couldn't keep pace.
The Giants (1-4) lost running back Saquon Barkley (ankle), quarterback Daniel Jones (concussion) and receiver Kenny Golladay in the first half.
Justin Fields passed for 111 yards and a touchdown to lead the visiting Chicago Bears to a victory over the Las Vegas Raiders.
Fields completed 12 of 20 passes in his first start since being named the permanent starter for the Bears (3-2), who got plenty of help from a ground game that rolled up 143 yards.
Khalil Herbert, a rookie from Virginia Tech, led the way with 75 yards on 18 carries, while Damien Williams rushed for 64 yards and a touchdown.
Roquan Smith had 10 tackles and Khalil Mack had eight tackles and a sack to lead Chicago's defence, which held Las Vegas, which was averaging 406.5 yards in total offence, to just 259 yards.
Tom Brady closed in on his 600th NFL touchdown pass as he led the Tampa Buccaneers to a 45-17 thrashing of the Miami Dolphins.
The 44-year-old threw five touchdowns and the Super Bowl champions scored six in total as they improved their season record to 4-1.
Brady, the NFL's record holder, has 596 career touchdowns after throwing two apiece to Antonio Brown and Mike Evans and one to Giovani Bernard on Sunday.
Aaron Rodgers moved his way up to fifth in the list as his Green Bay Packers edged to a rollercoaster 25-22 victory over the Cincinnati Bengals.
The 37-year-old threw two touchdown passes to take his career tally to 422 and move above the retired Philip Rivers.
But the game ended in drama as, with the score tied at 22-22, both teams missed field goals in the closing stages of the fourth quarter and at the start of overtime.
Eventually, Packers kicker Mason Crosby found his range as he slotted over from 49 yards with two minutes remaining to move Green Bay to 4-1.
Ben Roethlisberger - eighth on the quarterback passing list with 402 - silenced some of his critics as he led the Pittsburgh Steelers to a 27-19 triumph over the Denver Broncos.
The 39-year-old had struggled as the Steelers lost three straight games but threw touchdowns to Diontae Johnson and Chase Claypool to see off Denver.
The Jacksonville Jaguars slipped to 0-5 after a bad week ended with a 37-19 defeat at home to the Tennessee Titans.
Head coach Urban Meyer was warned by franchise owner Shad Khan he needed to "regain our trust and respect" after a video of the 57-year-old at a bar went viral following their last defeat.
And Meyer watched his side fail to deal with Titans star running back Derrick Henry, who rushed for three touchdowns.
The winless Detroit Lions lost to a last-second field goal for the second time this season as Greg Joseph's 54-yard effort secured a 19-17 success for the Minnesota Vikings.
The New England Patriots also won thanks to a last-gasp field goal as they saw off the Houston Texans 25-22.
Jameis Winston threw a 49-yard 'Hail Mary' to Marquez Callaway during the New Orleans Saints' 33-22 victory over the Washington Football Team, while the Philadelphia Eagles beat the Carolina Panthers 21-18.
Rookie tight end Kyle Pitts scored his first NFL touchdown as the Atlanta Falcons secured their second win of the season by beating the New York Jets 27-20 in London.
The NFL returned to the UK's capital for the first time in two years and Pitts produced a breakout game at Tottenham Hotspur Stadium, where he had nine catches in all for 119 yards.
