SANTA CLARA, Calif. -- The Carolina Panthers set the tone early on defense Sunday in their season opener against the San Francisco 49ers at Levi's Stadium.

Defensive end Wes Horton had a blind-side strip-sack of 49ers quarterback Brian Hoyer, and defensive tackle Star Lotulelei recovered his fumble at San Francisco's 42. Three plays later, quarterback Cam Newton threw a 40-yard touchdown pass to wide receiver Russell Sheppard, giving Carolina a 7-0 lead with 3:00 still left in the first quarter.

There were more sacks and big defensive plays to come for the Panthers, and by the end of the day they celebrated a 23-3 victory against the 49ers in their first trip to Levi's since a loss to Denver in the Super Bowl two seasons ago.

"I'm just excited for our defense. I'm excited for this group, I'm excited for this team, our room especially, and I think we came out and had a good start," Lotulelei said. "Just got to keep going up."

Newton, who underwent offseason shoulder surgery and saw little game action in preseason, was clearly rusty but still threw two touchdown passes, Graham Gano kicked three field goals, and Carolina's defense dominated.

Carolina had four sacks, one each by Horton and outside linebackers Thomas Davis and Shaq Thompson and half a sack each by defensive end Julius Peppers and Lotulelei. Middle linebacker Luke Kuechly intercepted a pass. Carolina turned both turnovers it forced into touchdowns. The Panthers also stopped the 49ers on three of four fourth-down attempts.

"Our D line was tremendous," Davis said. "Those guys did a great job of creating a lot of pressure, making our job a lot easier on the back end."

The Panthers ruined the debut of 49ers first-year head coach Kyle Shanahan, whose offense failed to produce a touchdown.

"It was disappointing," Shanahan said. "But whether it was the first, last or any one I have the rest of my career, it was disappointing. I don't think it matters that it was the first. Anytime you lose and lose that way, it's frustrating and disappointing. I'll feel that all day today and all night and I'm sure our players will too."

Newton completed 14 of 25 passes for 171 yards with a touchdown pass to Sheppard and a 9-yard scoring strike to running back Jonathan Stewart. He was intercepted once.

Panthers rookie running back Christian McCaffrey rushed for 47 yards with a fumble on 13 carries and caught five passes for 38 yards in his NFL debut.

"I didn't play as well as I would've liked, but anytime you can get a win we're happy," McCaffrey said.

Hoyer went 24 of 35 for 193 yards and an interception in his 49ers debut. Pierre Garcon had six catches for 81 yards in his first game for San Francisco.

"It was probably as disappointing as it could have been," Hoyer said. "When you get it handed to you like that, you just have to go figure out what's wrong, make the corrections and move on."

The Panthers struck first when Newton hit Sheppard down the left sideline. Sheppard broke Jaquiski Tartt's tackle attempt at the 15 and sprinted into the end zone.

The Panthers increased their lead to 10-0 with 3:23 left in the first half on Gano's 39-yard field goal. Once again, Carolina's defense made a big play to set up the score.

Facing fourth-and-4 from the Carolina 44, Hoyer dropped back to pass but was sacked by a blitzing Davis for an 8-yard loss. Six plays later from the 49ers' 21, Newton overthrew wide-open tight end Ed Dickson in the end zone, and the Panthers settled for a field goal.

"The quarterback obviously is still working on his timing," Panthers head coach Ron Rivera said of Newton. "He missed a couple, and he knows it. He's upset with himself. Had to talk him off a ledge. He's focusing on what he needs to get done. The nice thing is all the other guys are rallying around him. They understand he's a little rusty."

Carolina got the ball back when Horton and Lotulelei combined to stuff 49ers fullback Kyle Juszczyk for no gain on fourth-and-1 at the Panthers' 45.

The Panthers marched 37 yards in eight plays for Gano's 36-yard field goal as time expired in the first half.

On the first drive of the second half, Kuechly intercepted Hoyer's pass over the middle intended for tight end George Kittle and returned it 23 yards to the 49ers' 28. That set up Newton's 9-yard touchdown pass to Stewart as Carolina increased its lead to 20-0 with 11:24 left in the third quarter.

"That's one of their routes that we've seen the past however many years in Atlanta and Cleveland, where Shanahan's been (an offensive coordinator)," Kuechly said. "I finally was able to get one. They do a good job sucking you up on play action and hitting it behind you. We did a good job of getting some guys in his face."

Gano made it 23-0 with a 20-yard field goal with 3:11 left in the third quarter. The 49ers scored with eight seconds left in that quarter on Robbie Gould's 44-yard field goal.

The 49ers had fourth-and-goal from the 1 midway through the fourth quarter, but Davis stopped Carlos Hyde for no gain.

"As an offensive lineman, you want your head coach to do that," 49ers center Daniel Kilgore said of going for it four times on fourth down. "It's very upsetting when you don't get the job done."

NOTES: Panthers QB Cam Newton wasn't available to talk to the reporters after the game because he had to take a random drug test, according to the team. ... 49ers starting OLB Reuben Foster, a rookie first-round pick out of Alabama, injured his right ankle with 3:33 left in the first quarter while making a tackle and was carted to the locker room. Foster walked back to the bench with a slight limp early in the second quarter, but did not return to action. "It was more optimistic than it (initially) looked," 49ers head Kyle Shanahan said. "Still got to do more tests." Ray-Ray Armstrong replaced him in the lineup. ... 49ers FS Jimmie Ward (strained hamstring) was inactive and Jaquiski Tartt started in his place. ... Panthers K Harrison Butker, one of two kickers on Carolina's roster, was inactive. Graham Gano handled all the kicking duties.