Jake Delhomme, whose downward spiral began with a playoff loss at home against Arizona last season, threw a 50-yard touchdown pass before leaving with a chest injury and Jonathan Stewart ran for two scores in Carolina's 34-21 victory that dropped the Cardinals to 1-3 at home this season.
The Panthers, in a turnover-free performance, rolled up 270 yards on the ground against what had been the No. 1 rushing defense in the NFL.
Arizona's Kurt Warner was intercepted five times and fumbled the ball away once. Julius Peppers returned one of the picks 13 yards for a touchdown.
Coincidentally, Delhomme was intercepted five times in the Panthers' 33-13 home playoff loss to the Cardinals. He had a league-worst 13 picks this season entering Sunday.
His statistics weren't impressive, but he made no big mistakes and the Panthers' punishing ground game did the rest.
Delhomme was 7 of 14 for 90 yards, including a 50-yard TD pass to Steve Smith, the first scoring pass to a wide receiver for the Panthers this season.
DeAngelo Williams rushed for 158 yards on 23 carries, including a 77-yarder to set up Stewart's 10-yard touchdown run that put Carolina (3-4) up for good 14-7 on the first play of the second quarter. Stewart gained 87 yards in 17 attempts.
Delhomme was hurt on a hard hit by Arizona's Chike Okeafor and Darnell Dockett with 5:59 left in the third quarter. He got to his knees, then slowly walked off the field, but was back for the next series before leaving the game for good.
It was a near-exact reversal of roles with the favored Cardinals on a three-game winning streak and coming off a Sunday night road victory over the New York Giants. Instead of keeping the momentum going, Arizona has lost as many home games as it did all of last season.
The Cardinals (4-3) remained in first in the NFC West because San Francisco lost at Indianapolis, but the ugly performance often drew boos from the capacity crowd.
Each team had a touchdown on its first possession. Stewart scored on a 6-yard run, then Warner threw 14 yards to rookie LaRod Stephens-Howling for his NFL touchdown.
With the Panthers leading 21-7, Arizona Dominique Rodgers-Cromartie bit on Delhomme's pump fake, freeing Smith to run alone downfield on a 50-yard touchdown pass play and it was 21-7 with 7:33 left in the half.
Five seconds later, on the Cardinals' next play from scrimmage, Peppers stepped in Warner's way and picked off the short pass, running untouched for the score that made it 28-7.
The Cardinals cut it to 28-14 and 31-21 but could get no closer as John Kasay kicked field goals of 35 and 31 yards in the fourth quarter.
Arizona's Anquan Boldin played despite an ankle injury that limited him in practice all week. However, he aggravated the injury in the third quarter, left the game and did not return. He did catch two passes to make him the Cardinals' career leader in receptions.