DENVER — Peyton Manning joined Brett Favre in the NFL’s most exclusive of clubs with his 500th touchdown pass Sunday when the Denver Broncos handed the Arizona Cardinals their first loss, 41-20.

Manning finished with four TD throws, moving him within five of Favre’s record 508.

Manning found tight end Julius Thomas twice in the end zone, including the touchstone touchdown, a 7-yard dart in the first quarter.

Yet, it was wide receiver Demaryius Thomas who had the biggest day for the Broncos (3-1) with eight catches for a team-record 226 yards and two TDs. That beat Shannon Sharpe’s mark of 214 yards set against Kansas City in 2002.

Demaryius Thomas caught touchdown passes of 31 and 86 yards — and his 77-yard TD was nullified by left tackle Ryan Clady’s chop block in the third quarter. Arizona (3-1) lost for the first time and saw quarterback Drew Stanton leave with a possible concussion.

Manning finished 31 of 47 for 479 yards, four TDs and two interceptions. Emmanuel Sanders caught seven passes for 101 yards.

Stanton, subbing for Carson Palmer again, was knocked from the game on a hard hit by Von Miller in the third period and Logan Thomas came in for Arizona (3-1). Stanton finished 11 of 26 for 118 yards.

After getting sacked twice on his first drive and throwing two incompletions on his second, Thomas threaded a pass through linebacker Nate Irving’s grasp. It landed in the arms of running back Andre Ellington for a stunning 81-yard score that made it 24-20 late in the third quarter.

That ended up being Thomas’ only completion in eight attempts.

Brandon McManus, whose solid start convinced the Broncos that they should release the suspended Matt Prater, made it 27-20 when his 41-yard field goal bounced off the left post and through the uprights.

Earlier, McManus was good from 44 yards, but wide left from 53.

Manning then threw his fourth TD and second to Julius Thomas, a 12-yarder that made it 34-20. It was the tight end’s seventh TD grab of the season.

With Montee Ball sidelined with a groin injury, Ronnie Hillman ran for 64 yards on 14 carries. Rookie Juwan Thompson bullied his way in from 8 yards to cap the scoring.

Broncos linebacker Danny Trevathan made his 2014 debut after breaking his left leg in the preseason. He led the Broncos with seven tackles, six solo.

Manning’s 500th TD throw came in his 244th career regular season game, 49 fewer games than it took Favre. It came against two of his mentors: Arizona coach Bruce Arians and Cardinals assistant head coach Tom Moore. Arians was Manning’s first position coach in 1998 and Moore was his offensive coordinator during his entire time in Indy.

Knowing him better than any other team does, it wasn’t surprising the Cardinals came up with two interceptions of Manning, either. What was a big surprise was 300-pound defensive end Calais Campbell snatching Manning’s screen pass and rumbling to the 5, where Manning tripped him up. Ellington took it in from there to pull Arizona to 14-13.

Campbell later left with a right knee injury.

Manning had his own quick score up his sleeve. He saw cornerback Antonio Cromartie lined up 1 on 1 on Demaryius Thomas. Manning hit his big receiver in stride at the 40 and Thomas sped into the end zone with an 86-yard score that gave Denver a 21-13 halftime lead.

On the final play of the first half, Broncos slot receiver Wes Welker broke Rod Smith’s mark for most catches by an undrafted player. His 850th career grab, his third of the game, covered 5 yards.