Patrick Mahomes and the Kansas City Chiefs hit the road to begin the 2022 NFL season when they face Kyler Murray and the Arizona Cardinals in one of the marquee matchups of the opening NFL betting weekend. 

Mahomes’ Chiefs went 12-5 last season but missed out on a third-consecutive Super Bowl berth. Murray’s Cardinals went 11-6, a three-win increase from the year before, and inked their QB to a massive extension this offseason. Each team has high expectations for 2022. 

Bookies.com NFL handicapper Adam Thompson - who has hit 62-64% of his NFL picks three years running - reveals his plays for the showdown in the desert. 

And don't forget, if you are a bettor in Kansas you need to check out our Kansas promo codes page for the latest betting deals and offers in the Sunflower State, following the launch of legal sports betting on Sept. 1. Scroll down for more information on that and our best Chiefs vs. Cardinals picks.

Chiefs vs. Cardinals Point Spread

No Tyreek Hill, no problem for a Chiefs offense that added JuJu Smith-Schuster and Marques Valdez-Scantling in the offseason, and finally has a healthy Clyde Edwards-Helaire in the backfield. CEH should be a huge boon here against a defense that could be a bottom-five unit vs. the run. 

Murray reunited with former college running mate Marquis Brown; expect those two to have a big opening game. But there are more questions on Arizona’s defense than there are on KC’s. Arizona was a horrible home-covering team last season. Lay the points on the road Chiefs here as one of your Chiefs vs. Cardinals best bets. 

Chiefs vs. Cardinals Over/Under

The 53.5-point total for Chiefs vs. Cardinals is, rightfully so, the highest O/U of NFL Week 1. But is it high enough? I don’t think so. Defenses typically have an edge early in the season as fewer marquee offensive players see any preseason action. That shouldn’t matter here. 

Neither team is going to rely much on defensive prowess here. The Chiefs’ last seven season openers have finished Over, and it’s hit in seven of the last seven Arizona games as a home dog. Back the Over on the week’s highest total when making your Chiefs vs. Cardinals best bets for Sunday.

Chiefs vs. Cardinals Moneyline

The Cardinals can, and will, score points. But they also have little chance of slowing Mahomes and the Chiefs offense, even with no Hill causing havoc. Mahomes is 26-7 straight-up on the road in his career. He won’t be fazed by a Week 1 road crowd. 

Chiefs all day here for our Chiefs vs. Cardinals NFL best bets ahead of Sunday. 

Best Chiefs vs. Cardinals Player Props

Patrick Mahomes, Over 2.5 TDs

Odds:

Mahomes comes ready for Week 1. Last season he opened the year with four games of three TDs or more. The last time he didn’t toss at least three touchdowns in the opening game? Never. He’s done it every, single year of his career. 

The Cardinals last season allowed 30 passing TDs; only three teams allowed more than 31. Back Mahomes to get it done again in Week 1 with the Over at BetMGM as one of your Cardinals vs. Chiefs best bets. 

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Travis Kelce, Over 75.5 Receiving Yards

Odds:

We mentioned Mahomes coming out hot. When he does, Kelce is his main dog. Last year, Kelce caught at least six passes in each of the first three weeks, and 76+ yards in all three, averaging 96.3 ypg. 

Arizona last season was among the best at ensuring tight ends didn't go off. But without Tyreek Hill to fall back on, Mahomes’ security blanket should be in line for another big Week 1. Back Kelce and the Over with these odds at DraftKings as one of your Chiefs vs. Cardinals best bets. 

Can I bet on the Chiefs in Kansas?

Yes! Starting Sept. 1, Kansas sports betting is legal in the Sunflower State and readily available for Kansas bettors. 

Many of the top Kansas betting apps – BetMGM, Caesars Sportsbook, DraftKings, FanDuel, PointsBet and Barstool – will take NFL betting plays in time for Week 1. The best signup deals are available now, and some of them are outrageously good. Just hit 'Bet Now' on any of the green buttons on this page to access the deals. 

Alternatively, click on any of the following links, and then hit 'Bet Now' to place your wagers.