GLENDALE, Ariz. -- Maybe they should call the place Manning Manor.
On the field where little brother Eli led the New York Giants to a Super Bowl triumph two seasons ago, Peyton Manning threw four touchdown passes in his first game there, three in the second quarter, to power the Indianapolis Colts past Kurt Warner and the turnover-plagued Arizona Cardinals 31-10.
The Colts' quarterback completed 24 of 35 for 379 yards with one interception.
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"He knew what plays to call at the right time," Arizona defensive tackle Darnell Dockett said, "and we couldn't stop them."
The game featured two of the most prolific quarterbacks in NFL history in Manning and Warner. But while Manning's line gave him time to carve up the Cardinals' defense, the 38-year-old Warner was under a fierce rush all night long.
"I think that was the key to the game, personally," said Colts defensive end Dwight Freeney, who was in Warner's face throughout before leaving with a quadriceps injury late in the third quarter. "Our offensive line did a great job protecting Peyton, giving him time to find his receivers. And then I think collectively as a defense we put pressure on Warner and had him uncomfortable all game."
It didn't help that Arizona turned the ball over twice deep in Indianapolis territory, either.
"Against good football teams, ones that play as well as they did tonight offensively, you can't make those mistakes," Cardinals coach Ken Whisenhunt said, "and that's what we did."
Warner was 30 of 52 for 332 yards and one score but was picked off twice.
Despite being on the field for 84 plays in the Colts' victory at Miami on Monday night, the Indianapolis defense was tough. After allowing 239 yards on the ground against the Dolphins, the Colts allowed 24 yards in 12 attempts against Arizona.
Of course, the Cardinals all but abandoned the ground game when they fell far behind, a situation that the Colts' defensive line relished.
"We kind of lick our chops," Freeney said. "This is what we want."
Indianapolis safety Antoine Bethea recovered a fumble at the 5 to stop one Arizona drive and intercepted a deflected pass in the end zone to thwart another.
Manning had four TD passes in a game for the 18th time, moving him ahead of Johnny Unitas into third on the NFL career list, behind Dan Marino's 21 and Brett Favre's 20.
Manning topped 300 yards passing for the third time in three this season, giving him 50 for his career.
"The thing is that we constantly have to make certain that we don't take it for granted," coach Jim Caldwell said of Manning's performances. "He's had some just unbelievable games. ... I think he amazes us every time he does it, but he does it so often if you don't watch yourself you can think that it's commonplace, but it certainly is not."
Manning started slow but sliced and diced the Cardinals with a show of precision in the second quarter.
"We were kind of figuring things out as we went along," he said. "Once we got into a comfort zone, we really executed from there."
Manning added a 3-yard TD toss to Joseph Addai in the third quarter to make it 28-10.
The Cardinals, up 3-0 early, drove deep into Indianapolis territory but Tim Hightower fumbled at the 5.
The Colts (3-0) then went 95 yards in 11 plays for the touchdown that put them ahead for good.
"That just kind of took the wind out of us," Whisenhunt said.
Wayne made a one-handed grab of Manning's pass at the pylon on a 20-yard play that put the Colts up 7-3 with 9:04 left in the half.
"Can't draw that up," Manning said. "You know he's capable of making those plays. ... Those are the plays we expect him to make."
After Indianapolis stuffed Arizona's offense, the Colts went 57 yards in six plays, Manning throwing 10 yards to Clark to make it 14-3 with 5:49 to go in the half.
The prettiest score came when Manning lofted a pass down the sideline into the outstretched arms of Garcon on a 53-yard scoring play that made it 21-3 with 1:52 to go in the half.
Warner drove the Cardinals (1-2) to the Indianapolis 1-yard line in the final seconds of the half. He threw to Steve Breaston at the goal line but Melvin Bullitt didn't allow the receiver into the end zone.
Arizona took the second half kickoff and went 73 yards in eight plays, with Warner throwing 10 yards to Anquan Boldin for the touchdown to cut it to 21-10 with 10:50 to play in the third.
But a 72-yard pass play from Manning to rookie Donald Brown set up the 3-yard TD toss to Addai to boost the lead to 28-10 with 2:26 left in the quarter.
Freeney limped off the field at the end of the third quarter with a right leg injury and did not return. He said he "felt something pop" in his right quadriceps and planned to undergo an MRI Monday or Tuesday.
Arizona, 8-2 at home last season, fell to 0-2 there this season, with echoes of boos through what was left of the crowd as Warner was sacked for a 28-yard loss on fourth down with about 6½ minutes to play.
- Dockett left with an ankle injury in the first quarter but returned and played despite the injury.
- The Cardinals have a bye next week.
- The Colts rolled up 505 yards.
- Two injured Indianapolis defensive starters -- MLB Gary Brackett (left knee) and CB Kelvin Hayden (sore hamstring) -- were inactive.