The Panthers opened up their regular season on the road against the Cardinals. Cam Newton came into the game amid numerous questions and after a mixed-performance 1–3 preseason. Newton surprisingly threw for 422 pass yards, an NFL record for a rookie in his first start. The Panthers came into the 3rd quarter leading 14–7, Newton having thrown 2 touchdown passes, each to Steve Smith. The Panthers came into the 4th quarter tied at 21. On a 4th & 13 at the Cardinals 47-yard line, the Panthers were forced to punt. Patrick Peterson returned the ball into the endzone for an 89-yard touchdown return. With 1:19 left, 4th and 5, at the Cardinals 6-yard line, game on the line, Cam Newton threw a short 4-yard pass to Mike Goodson which wasn't enough for the Panthers despite an amazing debut by Panthers rookie QB Cam Newton. With the loss the Panthers fell to 0–1 and lost their 3rd consecutive regular season opener.
The Panthers' first home game of the season was a duel against the defending super bowl champions, the Green Bay Packers. Cam Newton threw for once again another 400+ yard game, becoming the first rookie ever to do so and only the 6th quarterback in NFL history to accomplish such a feat. Newton picked up where he left off against the Cardinals with an early score with 9:26 left in the 1st quarter of the game. The Panthers would lead 13–7 at halftime, stunning the defending Super Bowl champions. However, Green Bay would come back when Aaron Rodgers threw a 49-yard touchdown pass to a wide-open Greg Jennings to put the Packers up 14–13. A big game-changer was when there was 9:31 left in the 3rd quarter of the game. Cam Newton found Steve Smith, but Smith fumbled the football and Charles Woodson picked it up. Another big game changer was on a 4th and 4 at the Packers 6-yard line with 3:23 left in the game, score being 23–16 Packers, Cam Newton tried to scramble for the first down, but was 2 yards shy. The Packers would go on to win the game, 30–23, a much closer game than expected, but the Panthers still fell to 0–2 on the season.
The Panthers came into Week 3 in need of a win in order to save their season. This game would be against the Jacksonville Jaguars, who had gone 8–8 last season and were 1–1 to start the season in 2011. The Jaguars would bench Luke McCown and start rookie Blaine Gabbert after McCown's disastrous 4 interceptions in a devastating 32–3 loss to the New York Jets. The Panthers would start the game by sacking Gabbert and getting a safety, to lead 2–0.
With the score 5–3, one of the more memorable moments during the season occurred. A heavy rain started coming down, blanketing the stadium and flooding the concrete decks. Players slipped and slid all over the place, water going everywhere. Most dramatically, the excess water on the stadium's upper deck poured onto the lower deck which poured onto the field. Although the field had a drainage system, it was not designed for such an amount of water at once. Moments later, a Gabbert pass was picked off by Carolina's Sherrod Martin. However, for those watching the game on TV it was difficult to tell who picked the pass off or where he was. The reason was CBS' main camera feed was covered with so many raindrops that identifying specific players on the field was nearly impossible. Viewers, therefore, had to rely on the call from play-by-play announcer Spero Dedes as to exactly what was happening on the play. Subsequent replays gave them a clearer picture.
With 0:06 left in the 1st half, Blaine Gabbert threw a 36-yard touchdown pass to Mike Thomas which was both the first career touchdown pass by Blaine Gabbert and the first touchdown pass for the Jaguars in the 2011 season. Jacksonville would go up 10–5 at halftime, however, Carolina would come back.
With 6:05 left in the 4th quarter, and the rain not coming down anymore although the field, players, and fans were still soaked, Cam Newton finally found Steve Smith for a gain of 13 yards. On the same drive, with 4:27 left, on a 3rd and 2, Cam Newton found his new tight end, Greg Olsen, for a 16-yard touchdown pass to put the Panthers up 14–10. They would get the 2-point conversion which would put them up 16–10. Then, at the Panthers 35-yard line, 0:06 remaining on the game clock, the last play of the game, Blaine Gabbert's pass was tipped and incomplete, not only was it the Panthers' first win of the season, it was also the first time since 2008 the Panthers defeated an AFC team as well as the first time tell won a game in September, this then put them at 1–2.
In order to keep their season alive, the Panthers were in need of a win against the Bears to qualify for their first 2–2 or above start since 2008. Cam Newton threw for another 374 pass yards, which would be the highest total he would end up throwing for the rest of the season. Things started rough for the Panthers when Newton threw a pass to D.J. Moore which was taken back the other way for a Chicago Bears touchdown which put the Bears up, 10–3. Panthers now trailing 17–10, on a 4th and 5, forced to punt, Devin Hester beats out the Panthers special teams' for a 69-yard punt return, which would break the NFL record for punt return touchdowns (11). At halftime, the Panthers were trailing 24–20. The third quarter was scoreless. But in the fourth quarter, with 14:17 remaining on the game clock, Jay Cutler threw a pass to Charles Godfrey for an interception which they would get a field goal out of. With 1:55 left on the game clock, Panthers trailing by 1, 23–24, on a fourth-and-10 at their own 42, Cam Newton threw a deep pass to Legedu Naanee which was incomplete. Matt Forte basically sealed the deal on the very next play from the Bears' 43 when he ran for 40 yards down to the Panthers' 3. The Bears would punch it in and would go on to win the game, 34–29. For the first time in his career, Cam Newton was nominated for the Pepsi Rookie Of The Week awards. With the loss, the Panthers fell to 1–3.
The Panthers came into Week 5 again craving a win to get their season back on track. This time they were facing the former super bowl champions, the New Orleans Saints. The Saints were leading 10–0 with 3:04 left in the first quarter when Cam Newton threw a pass to wide receiver Steve Smith for a 54-yard touchdown after the touchdown Roman Harper was called for unnecessary roughness in the endzone. There would be a short fight after the play, and Olindo Mare would miss the extra point, it being blocked. With 4:01 left in the second quarter, the Panthers were trailing 17–6. Not when DeAngelo Williams took a left pitch from Cam Newton for a 69-yard score, Williams' first touchdown since 2009. Right before halftime, with 0:10 left, Sean Payton was trying to get the field goal unit out on the field for a John Kasay 46-yard field goal. Ron Rivera took a timeout because he thought he had too many men on the field, which would cost them a field goal which put the Saints up, 20–13. With 2:36 left in the third quarter, on a 2nd and 8, score 23–20 Saints, Drew Brees was intercepted by Sherrod Martin. Off of the interception, with 12:40 left in the game, on a 3rd and goal, Newton found Greg Olsen for a 5-yard touchdown to put the Panthers up 27–23. With 0:56 left in the game, Brees threw a short pass to Pierre Thomas for a six-yard score. Saints go up, 30–27. With 0:27 left, on a fourth-and-10, Cam Newton's pass is incomplete, intended for Greg Olsen, but there was a pass interference call on Roman Harper which set up a Panthers first down. Then, on a 3rd and 12 with 0:05 remaining, Cam Newton's pass, intended for Steve Smith is incomplete. With the close loss the Panthers fell to 1–4 on the season, though only being outscored 119–132 on the season.
With the loss, the Panthers fell to 1–5.
The Panthers came into this game with a 1–5 record, hoping to come back and fight to stay in the race for the playoffs. The Panthers held the lead just about the whole game as Cam Newton had 256 passing yards (& tied Vince Young's record for Most Rush TD by QB in Single Season for a rookie) for a Carolina win. With the win, the Panthers rose to 2–5.
The Panthers almost sent the game to overtime, however, Olindo Mare missed a 31-yard field goal. With the loss, the Panthers fell to 2–6.
With the loss, the Panthers fell to 2–7.
Carolina Panthers at Detroit Lions
|1||3:55||CAR||Olindo Mare 27 yard field goal||Panthers 3–0|
|1||:35||CAR||Steve Smith 15 yard pass from Cam Newton (Olindo Mare kick)||Panthers 10–0|
|2||14:04||DET||Kevin Smith 28 yard pass from Matthew Stafford (Jason Hanson kick)||Panthers 10–7|
|2||13:50||CAR||Kealoha Pilares 101 yard kickoff return (Olindo Mare kick)||Panthers 17–7|
|2||9:32||CAR||Cam Newton 11 yard run (Olindo Mare kick)||Panthers 24–7|
|2||2:57||DET||Titus Young 3 yard pass from Matthew Stafford (Jason Hanson kick)||Panthers 24–14|
|2||:00||CAR||Olindo Mare 31 yard field goal||Panthers 27–14|
|3||10:28||DET||Nate Burleson 16 yard pass from Matthew Stafford (Jason Hanson kick)||Panthers 27–21|
|3||5:57||DET||Tony Scheffler 17 yard pass from Matthew Stafford (Jason Hanson kick)||Lions 28–27|
|4||8:02||DET||Kevin Smith 4 yard run (Jason Hanson kick)||Lions 35–27|
|4||4:59||CAR||Cam Newton 4 yard run (Steve Smith pass from Cam Newton)||Tie 35–35|
|4||2:32||DET||Brandon Pettigrew 7 yard pass from Matthew Stafford (Jason Hanson kick)||Lions 42–35|
|4||2:00||DET||Kevin Smith 19 yard run (Jason Hanson kick)||Lions 49–35|
With the surprising loss, the Panthers fell to 2–8 but Cam Newton broke Vince Young's record for Most Rush TD by QB in Single Season by a rookie.
With the win, the Panthers improved to 3–8 and would secure the Colts' 0–4 record against the NFC.
Cam Newton broke Steve Grogan's record for Most Rush TD by QB in Single Season (a record that stood for 35 years). With the win, the Panthers improved to 4–8.
With their 4th straight loss to the Falcons, the Panthers fell to 4–9 securing them their second consecutive losing season.
With the win, the Panthers improved to 5–9. Also it was the first time in franchise history they defeated the Texans.
Tampa Bay Buccaneers at Carolina Panthers
|1||10:12||CAR||DeAngelo Williams 8 yard run (Olindo Mare kick)||Panthers 7–0|
|1||8:27||CAR||Olindo Mare 21 yard field goal||Panthers 10–0|
|2||14:07||TB||Arrelious Benn 4 yard pass from Josh Freeman (Connor Barth kick)||Panthers 10–7|
|2||13:06||CAR||Brandon LaFell 91 yard pass from Cam Newton (Olindo Mare kick)||Panthers 17–7|
|2||5:33||TB||Connor Barth 42 yard field goal||Panthers 17–10|
|2||:25||CAR||Olindo Mare 19 yard field goal||Panthers 20–10|
|3||11:55||CAR||DeAngelo Williams 22 yard run (Olindo Mare kick)||Panthers 27–10|
|3||3:24||CAR||Jonathan Stewart 11 yard pass from Cam Newton (Olindo Mare kick)||Panthers 34–10|
|3||:24||CAR||Cam Newton 49 yard run (Olindo Mare kick)||Panthers 41–10|
|4||14:53||CAR||Jeremy Shockey 8 yard pass from Cam Newton (Olindo Mare kick)||Panthers 48–10|
|4||11:08||TB||Josh Freeman 1 yard run (pass failed)||Panthers 48–16|
With the win, the Panthers improved to 6–9 and swept the Buccaneers.
The Panthers lost to the Saints, 45–17, dropping their record to 6–10, instead of the hopeful 7–9. This was still an improvement from their 2–14 record last season. The Panthers were 6–0 when Cam Newton did not have any turnovers.