Wilson shook off two third quarter interceptions -- including one returned for a touchdown -- and outperformed Newton on a struggle-filled day for the Carolina offense, which finished with only 190 yards.
That included forcing Newton into an incompletion on a fourth-and-goal from the 1 with 3:47 left.
"Nothing can express it more than standing up on the goal line down there and finishing. That was awesome. It's what defensive players and coaches live for -- those challenges and opportunities -- and the guys came through in a big way."
Newton threw for a career-low 141 yards on 12-for-29 passing and he was sacked four times. He also ran for 42 yards.
"When you know what guys are doing and you still can't beat them, they're just good at what they do," said Newton, last year's No. 1 overall draft pick.
"Let's call a cat a cat and a dog a dog. They're a great defense. We knew what we they were going to do before the game even started."
The offense never found a rhythm while Newton was frequently off target, completing just three of 15 passes for 40 yards in the first half.
Carolina had two chances to take the lead in the final minutes Sunday, only to come away empty each time.
The game marked a homecoming of sorts for Wilson, who first gained acclaim as a quarterback at North Carolina State. He also played minor-league baseball in Asheville and Gastonia before returning to college football and finishing up at Wisconsin.
The rookie hadn't thrown for more than 160 yards in a game until Sunday, but didn't panic when he threw the two interceptions and bought time with his mobility on several plays.
"I felt like we had so much control there," Wilson said. "I made sure everyone was on the same page, and even changed the snap count a lot. We did a lot of great things today. ... Obviously, some of the penalties pulled us back, as did the turnovers, but we still did a lot of great things."
NOTES: The Panthers played without three starters: cornerback Chris Gamble, linebacker Jon Beason and offensive lineman Geoff Hangartner due to injuries. ... Newton targeted receiver Steve Smith a season-high 13 times. The previous high was 11 in the opener against the Tampa Bay Buccaneers. ... Seattle tight end Zach Miller had three catches for a season-high 59 yards, including a season-long 30-yard catch. ... Seattle's Sidney Rice had five catches for 67 yards.
Copyright 2012 by The Associated Press.