Newton was listed as inactive for the first time in his career.
The Panthers didn't want to run the risk of further damaging Newton's ribs, which were fractured when New England Patriots linebacker Jamie Collins kneed him in the back at the end of a 7-yard run in the third exhibition game.
Anderson is 18-25 as a starter, including 10-5 in 2007, when he made the Pro Bowl for the Cleveland Browns.
Newton did not practice Wednesday and was limited Thursday but did take all the repetitions during installation of the game plan.
Panthers coach Ron Rivera previously had said that Newton, who was a full participant in Friday's practice, would be a game-time decision for Sunday's contest.
Rivera made the decision to sit Newton on Saturday night after talking to team doctors, trainer Ryan Vermillion, offensive coordinator Mike Shula and others.
"And then I talked to Cam, who wasn't very happy about it,'' Rivera said. "He wanted to play so bad, in the worst way. The one thing the doctors stressed to me was if we could create one more opportunity he would be that much healthier.''
Rivera said he expected Newton to be ready to play in Week 2 against Detroit.
Newton did not talk to reporters after the game.
"Absolutely not,'' he said with a smile when asked if he could comment on the decision.
Backup quarterback Derek Anderson completed 24 of 34 pass attempts for 230 yards and two touchdowns in his first victory as a starter since the third week of the 2010 season for Arizona.
"I had a blast,'' Anderson said.