Newton was held out because of a rib injury suffered during the preseason, giving Anderson his first start since 2010 when played for the Arizona Cardinals.
The 10th-year pro had appeared in just four games and attempted only four passes over the previous two seasons playing behind Newton, who had started 48 consecutive games before learning Saturday night that coach Ron Rivera intended to sit him.
"He wasn't very happy about it. He wanted to play so bad, in the worst way," Rivera said. "The one thing the doctor stressed to me was that if we could create one more opportunity, he'd be that much healthier. That was the decision."
Despite rallying with two late touchdowns, it was an ugly debut for the Bucs (0-1) under coach Lovie Smith. The defense applied little pressure on Anderson and failed to force a turnover. And the offense, one of the worst in the NFL a year ago, showed few signs of improvement until midway through the fourth quarter.
"I've been through a lot of different things. I haven't been out there in four years. Just to play a solid football game and get a win was big for me," Anderson said.
"I prepared all week like I was going to start," he added. "I had a plan in mind, what I was going to do against different coverages, and went out there and tried to execute as best I can."
Carolina's defense did its part, too.
McCown, a career backup, was coming off his best season as a pro in throwing for 13 TDs versus one interception filling in for an injured Jay Cutler in Chicago a year ago.
On Sunday, he was 22 of 35 for 183 yards and two TDs. Much of his production came after the Panthers built a 17-0 lead midway through the third quarter.
"I made a couple bad decisions that hurt our team and put us in a bad situation. It's things that I can clean up and get better, so there's no need to focus on anybody else. ... Those are things I can correct, and we'll get better as we move forward," McCown said.
The Bucs got the ball back trailing by a field goal with 1:36 to go. But Kuechly, the 2013 NFL Defensive Player of the Year - forced Rainey to fumble after a short reception on the next play, spoiling any hopes for a comeback.
"We got ourselves in a hole in the first half, didn't do many things right," Smith said. "We talk about the turnover ratio, and we talk about everything that went wrong throughout the game. And at the end we had a chance to intercept a ball, were down three points and could have gone in for at least a field goal, and we (dropped) it."
Newton led a pair of lopsided victories over Tampa Bay a year ago, when the Panthers tied a franchise record with 12 wins. The first player selected in the 2011 draft posted career highs in completion percentage, touchdowns passing and passer rating. He injured his ribs Aug. 22 at New England, sat out Carolina's preseason finale and was limited in practice last week after initially saying he was confident he'd play.