DENVER — Quarterback Peyton Manning’s 500th career touchdown pass was just the beginning on a record-setting day for the Denver Broncos quarterback.

Manning hit the milestone with the first of his four scoring passes and he threw for a career-best 479 yards as the Broncos knocked the Arizona Cardinals from the ranks of the unbeaten with a 41-20 victory on Sunday.

“He’s not in the history books for nothing. The guy is awesome,” said Cardinals cornerback Patrick Peterson after Manning shredded Arizona’s fifth-ranked defense for a Denver franchise record 568 yards in total offense. “He just came out here and lit us up.”

The loss by the Cardinals, who finished the game with third string quarterback Logan Thomas playing in place of injured Drew Stanton, left Cincinnati as the NFL’s only undefeated team.

Manning had touchdown passes of 31 and 86 yards to wide receiver Demaryius Thomas and joined Brett Favre as the only players in NFL history to reach the 500 touchdown mark with a seven-yard strike in the first quarter to tight end Julius Thomas.

“Throwing touchdowns is a part of playing football, but I guess for me, I feel like throwing touchdowns has helped the teams I’ve been on win a lot of football games,” Manning said. “I don’t think I’ve thrown a lot of touchdowns that didn’t mean something.”

That sure was the case on Sunday and Manning’s favorite target, Demaryius Thomas finished with eight catches for a franchise record 226 receiving yards. Thomas eclipsed the previous high by Shannon Sharpe, who had 214 yards against Kansas City on Oct. 20, 2002.

“He works. He works, and he loves football,” Manning said. “I really appreciated the way he played today.”

Julius Thomas, who also caught a 12-yard touchdown pass in the fourth quarter, jogged back to Manning after the initial score and returned the ball to his quarterback as a keepsake. But Manning’s day, playing against an aggressive, pressing Arizona defense, was not always characterized by the quick, clean, accurate release that he demonstrated in his milestone scoring pass.

He had to shake off two interceptions, including one in the second quarter by defensive end Calais Campbell that set up running back Andre Ellington’s 5-yard touchdown.

“They were playing a lot of press coverage. It wasn’t a game where you were going to have a lot of easy runs,” Manning said. “We knew it was going to be a passing game. We knew there were going to be some incompletions. We knew there were going to be some kind of ugly series. But we thought if we stayed aggressive, we would get our big plays.”

Manning responded with three fourth-quarter scoring drives after Arizona had pulled to 24-20 on Logan Thomas’ 81-yard touchdown pass to Ellington late in the third quarter. He threw a 12-yard TD pass to Julius Thomas and running back Juwan Thompson added an 8-yard scoring run.

Brandon McManus added field goals of 41 and 44 yards for the Broncos in his first game since Denver decided to stick with him over longtime kicker Matt Prater, who was released Friday as he neared the end of a four-game suspension for violating the NFL’s substance abuse policy.

Stanton, starting his third game in place of Carson Palmer (shoulder nerve), completed 11-of-26 passes for 118 yards before leaving in the third quarter, shaken up after a third-down incompletion on a hit by linebacker Von Miller. The team said Stanton was being evaluated for a concussion.

In the third quarter, the Cardinals lost Campbell to a knee injury. He fell victim to a chop block for which tight end Julius Thomas was penalized.

The play, on a day in which the Cardinals lost several players to injury, infuriated Arizona coach Bruce Arians.

“I’ve been coaching for 37 years and it’s the dirtiest play I’ve ever seen in the National Football League,” Arians said. “It was a flat chop block that put him out of the game.”

Denver also lost a key player when running back Montee Ball went down with a groin injury in the third quarter.

What the Broncos said:

“That’s Peyton’s award. That’s Peyton’s moment. For me, it’s just a great thing for me to continue to find ways to help my team. I’m happy that Peyton trusts me to throw the ball down there in the red zone. Just keep that going and I’ll be happy.” — Tight end Julius Thomas, who made two touchdown receptions, including quarterback Peyton Manning’s 500th career TD pass.

What the Cardinals said:

“For me, it’s probably by far the worst game of my career. You look at it and you regroup from it. It’s one game out of the next 12.” — Cornerback Antonio Cromartie, who was beaten repeatedly by Broncos wide receiver Demaryius Thomas.

Two things we learned about the Broncos

1. The Broncos may have the most explosive passing game in the NFL, but concerns remain about their running game, which made little headway against the Cardinals. In addition, the Broncos may have to rely more heavily on backup running backs Ronnie Hillman and Juwan Thompson after starting tailback Montee Ball was knocked out of the game in the second half with a groin injury. The Broncos entered the game with the 27th-ranked rushing game in the league, and they produced 92 yards on 28 attempts (3.3-yard average).

2. Pass-rushing linebacker Von Miller appears to be getting back to his Pro Bowl form. He had a sack in a third consecutive game, his longest streak in two years. Miller’s season ended abruptly last December when he sustained a knee injury, but he appears to be back at full strength. With the offseason addition of free agent defensive end DeMarcus Ware, the Broncos now have two top pass rushers coming off the edges.

–WR Wes Welker had seven receptions for 58 yards, boosting his career reception total to 854, the most in NFL history by an undrafted player. He surpassed the previous mark held by Rod Smith, a member of the Broncos’ Ring of Fame, who had 849 catches during his distinguished career.

–LB Danny Trevathan had a team-leading seven tackles in his season debut. Trevathan returned from a leg fracture sustained in mid-August during a training camp practice.

–K Brandon McManus made two of three field goals in his first game since the Broncos opted to stick with him over veteran Matt Prater, who was released as he neared reinstatement from a four-game suspension. McManus converted attempts from 44 and 41 yards and was wide left with a 53-yard try. “Matt had a great career here,” McManus said. “I would still consider him a top-three kicker, (but) I don’t want to focus on his career. I am just trying to be myself and do the best job I can and hopefully help us succeed in the future.”

What we learned about the Cardinals:

1. Arizona rode a high-pressure, blitzing defense to a 3-0 start, but it proved to be susceptible to the big play against a well-protected, precision quarterback like Peyton Manning. Going forward, the Cardinals will have to strike a better balance. With their secondary left on island for much of the game, the Cardinals saw Manning pass for four touchdowns and a career-best 479 yards. The Broncos wound up with 568 yards of total offense, a single-game franchise high.

2. The Cardinals’ top two quarterbacks are injured, and rookie Logan Thomas may make his first career start next week against the Washington Redskins. However, Arizona’s receivers will need to support whoever is at quarterback with better play. The receiving corps made some critical drops against the Broncos, miscues that contributed to the Cardinals’ erratic offensive play. “It’s something we obviously have to be aware of throughout the course of the week this week and make sure we’re accountable to each other,” Cardinals wide receiver Larry Fitzgerald said.

–QB Drew Stanton sustained a concussion in the third quarter and left the game. He completed 11 of 26 passes for 118 yards while again starting in place of Carson Palmer, whose status remains uncertain because of a shoulder injury.

–DE Calais Campbell was lost to a right knee injury. The injury to Campbell came on a chop block that Cardinals coach Bruce Arians called the dirtiest play he had ever seen. Arians said Campbell could miss significant time.

–QB Logan Thomas, a rookie, could be in line to make his first career start next Sunday against Washington with Arizona’s top two quarterbacks injured. Thomas completed one of eight passes in relief of Drew Stanton, but it went for an 81-yard touchdown to RB Andre Ellington.

–CB Antonio Cromartie had a rough day against Broncos WR Demaryius Thomas, who beat him twice for long touchdowns and set a Broncos record for receiving yards with 226. “It’s probably by far the worst game of my career,” Cromartie said.