In the Panthers' home and season opener against the New York Jets, quarterback Sam Darnold and wide receiver Robby Anderson faced their former team for the first time.

Immediately after a Jets turnover on downs, Darnold found Anderson with a long pass for the first touchdown, but Santoso missed the extra point conversion wide left.

With Jets kicker Matt Ammendola's onside kick going out of bounds, the Panthers retained possession for the remainder of the game and won 19–14 to begin the season at 1–0.

The third quarter was scoreless; the Panthers came closest to scoring, but a 50-yard field goal attempt from Gonzalez was blocked by Carl Granderson and recovered by the Saints' Zack Baun.

On the next Eagles offensive play, Hurts overthrew Zach Ertz on a long pass down the left sideline and was intercepted by Jackson, who managed to keep both feet inbounds.

On the ensuing drive after the blocked punt, the Eagles took the lead with under three minutes left, with Hurts scoring his second rushing touchdown of the game before making the two-point conversion with a pass to Smith.

The Panthers' attempt to retake the lead resulted in Darnold's third intercepted pass of the game, this time by Steven Nelson, who stepped in front of Robby Anderson.

On the game's first play from scrimmage, Bashaud Breeland dove in front of Robby Anderson to intercept Sam Darnold, from which the Vikings scored with Greg Joseph converting a 25-yard field goal.

Joseph added another 25-yard field goal to close the deficit to one point before the Vikings regained the lead early in the second quarter with a touchdown pass from Cousins to Chris Herndon.

First, Cook scored on a 16-yard run after the initial ruling that he was down at the one-yard line was overturned; the two-point conversion was once again unsuccessful, as Jefferson was unable to stay inbounds to catch a pass from Cousins.

On the next Panthers play from scrimmage, D. J. Moore received a pass from Darnold and was tackled by Xavier Woods, who stripped away the football, which was subsequently recovered by Eric Kendricks.

On the opening play from scrimmage, Deion Jones tackled Chuba Hubbard for a two-yard loss and knocked the ball out, with Adetokunbo Ogundeji recovering the fumble.

[9] After Stephon Gilmore stepped in front of Kyle Pitts to intercept Ryan, the Panthers looked to close out the game but were forced to punt with under a minute left.

In the last minute of the first quarter, Brian Burns strip-sacked Mac Jones, with the ball being recovered by Frankie Luvu; on the ensuing drive, Zane Gonzalez converted a 39-yard field goal.

Later in the second quarter, Stephon Gilmore, who had been traded from the Patriots on October 6, intercepted Jones on a pass intended for Jakobi Meyers; from this, Gonzalez converted another field goal.

[13] After McCoy was unable to convert a quarterback sneak on fourth-and-one, resulting in a turnover on downs, Newton scored his second touchdown in as many snaps, with a two-yard pass to Robby Anderson.

While the other three NFC South teams lost their respective Week 10 games, the Panthers picked up a vital underdog[16] victory and improved to 5–5, matching their win total from each of the previous two seasons.

On the next drive, Cam Newton scored a one-yard touchdown run on his second effort with help from right guard Trent Scott after initially being stopped at the line of scrimmage.

In the final minute of the first half, the Dolphins were driving down the field in an attempt to further increase their lead before halftime, but a botched snap from Austin Reiter to Tagovailoa with 12 seconds left was recovered by Frankie Luvu.

As Luvu attempted to return the fumble recovery, he was tackled by Isaiah Ford with one second left, allowing Zane Gonzalez to kick a 41-yard field goal to end the first half.

[19] However, on his first drive of the game, Walker was forced to scramble out of the pocket and his underthrown pass intended for Ian Thomas was intercepted by Nik Needham, leading to the second of Sanders' field goals.

In the second quarter, Mykal Walker intercepted a pass from Newton intended for Ameer Abdullah and returned it 66 yards for a touchdown, before the Falcons bolstered their lead with a field goal from Younghoe Koo.

From this, Matt Ryan completed a touchdown pass to Hayden Hurst early in the fourth quarter, but the former was then unable to find an open receiver on the ensuing two-point conversion, which failed.

The Panthers closed the deficit to eight points as Walker completed a five-yard touchdown pass to Anderson, but the Falcons were able to retain possession for the rest of the game and win 29–21.

Early in the second quarter, Devin Singletary scored on a 16-yard run before the Bills doubled their lead with an touchdown pass from Josh Allen to Stefon Diggs.

In the fourth quarter, Ameer Abdullah scored on a 23-yard touchdown pass from Newton, but on the ensuing two-point conversation, the latter's rush attempt was stopped short by Tremaine Edmunds.

With under two minutes left in the first half, Tom Brady completed a touchdown pass to Cameron Brate but threw incomplete to Tyler Johnson on the two-point conversion that followed, though the Buccaneers still held a 19–6 lead at halftime.

Then, after Lirim Hajrullahu missed a 47-yard attempt early in the fourth quarter, Taysom Hill completed a 12-yard pass to Alvin Kamara for the Saints' first touchdown since Week 14.

Although Maher missed the extra point conversion, C. J. Gardner-Johnson intercepted Darnold on a pass intended for D. J. Moore in the final minute to seal the Saints' 18–10 win.

The Buccaneers then took the lead after driving almost the entire length of the field in under two minutes, as Tom Brady completed a touchdown pass to Le'Veon Bell with 15 seconds left before halftime.