Falcons quarterback Matt Ryan threw for a team-record 503 yards and four touchdowns as Carolina, Super Bowl finalists in February, crashed to a heavy loss at the Georgia Dome. To make matters worse for the Panthers, they lost Cam Newton to a head injury in the fourth quarter, the superstar quarterback taken to the locker room with suspected concussion.
It was also a bad night for 2015 Super Bowl champions the New England Patriots as their 100 per cent record went up in smoke in a 16-0 loss to the Buffalo Bills.
New England, who will be able to welcome back Tom Brady after his four-game suspension next week, had never before been shut out at Gillette Stadium since moving there in 2002 but the Bills did just that to move to 2-2 for the season.
Baltimore also saw their winning start to the campaign come to an end as they were edged out 28-27 by the Oakland Raiders, for whom Derek Carr threw for 199 yards and four touchdowns - three to wide receiver Michael Crabtree.
The Chicago Bears earned their first win with a hard-fought 17-14 triumph over the Detroit Lions but the Cleveland Browns crashed to a fourth successive loss after going down 31-20 to the Washington Redskins, who scored 14 unanswered points in the final quarter.
In London, the Jacksonville Jaguars made it two wins on the trot in their second home - this was their fourth game in the city in as many years - as they hung on to beat the Indianapolis Colts 30-27 in front of 83,764 fans at Wembley.
Also, the Houston Texans were 27-20 victors over the Tennessee Titans and the Seattle Seahawks edged out the New York Jets 27-17.
The Denver Broncos maintained their unbeaten record with a 27-7 win over the Tampa Bay Buccaneers.
New Orleans won for the first time this season, Drew Brees playing a key role as two touchdowns in the final four minutes enabled the Saints to cap a comeback from 13 points behind and sink the San Diego Chargers 35-34.
The San Francisco 49ers crashed to a third successive defeat, going down 24-17 to the Dallas Cowboys - after taking an early 14-point lead.
The Arizona Cardinals are also struggling - the 17-13 loss to the Los Angeles Rams was their third in four matches.