Early NFL Week 4 predictions and picks against the spread: Could backup RBs Alexander Mattison, Jamaal Williams, and Khalil Herbert step up?

If you're betting on 2022 NFL games -- whether props, DFS, point spreads, or moneylines -- here are our early NFL Week 4 predictions and picks.

Hello, everybody. Here’s an early look at our NFL Week 4 predictions and picks for all 16 games. The following betting odds are for picks against the spread, as well as moneylines based on DraftKings Sportsbook.

NFL Week 4 picks and predictions

Each week of the NFL season features the expected, the moderately unexpected, and the completely unexpected. When betting on point spreads and moneylines, we need to focus on the first two outcomes.

What are the highest-probability game scripts? Which interesting sub-plots could emerge? For example, we cannot anticipate when a little-used fullback will fall into the end zone twice in one half. But we can assess the likelihood that one team’s backfield will earn more scoring opportunities.

With that in mind, here are our preliminary assessments of how each game might proceed, including two major questions surrounding each team’s execution of its offense.

Cincinnati Bengals (-3) vs. Miami Dolphins

  • Date: Thursday, Sept. 29
  • Start time: 8:15 p.m. ET

The Dolphins have opened this season defeating the Patriots, Ravens, and Bills, which might make this the best Miami squad in more than 35 years. As strange as it sounds, a win over Cincinnati on Thursday could give them a clear path to an 11-0 record heading into a Week 13 showdown in San Francisco. (Yes, Miami’s schedule is about to get much easier.)

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But so much depends on the health of Tua Tagovailoa, who hurt his back in Sunday’s win. The NFL Players Association is investigating whether the league’s concussion protocols were followed when he appeared to be woozy and left the game after getting hit. These clouds of uncertainty hang over a betting line that could change by at least a couple points depending on how this shakes out. For now, I’m expecting a nail-biter.

Against-the-spread prediction: Dolphins
Moneyline winner: Bengals

New Orleans Saints (-2.5) vs. Minnesota Vikings

  • Date: Sunday, Oct. 2
  • Start time: 9:30 a.m. ET

The first game of the season in London features two teams going in opposite directions. Despite Jameis Winston’s broken ribs, the Saints recorded their most offensive yards of the season on Sunday (426) while their stout defense yielded only 293. Yet, they still lost, producing only 14 points despite a breakout performance by rookie Chris Olave.

Notably, Alvin Kamara has caught only five of 11 passes for a paltry 19 yards in his two contests, which is far below his career averages. There’s so much potential for this franchise, especially with a resurgent Michael Thomas. But Winston’s five interceptions and 11 sacks spell trouble for a team that needs to turn things around quickly.

For Minnesota, Dalvin Cook’s shoulder injury matters, and yet Alexander Mattison has proven to be a top-12 RB when called upon to start. The Vikings can win this one even if they’re not at their best; if their passing game clicks, it’ll be hard to stop them.

Against-the-spread prediction: Vikings
Moneyline winner: Vikings

Philadelphia Eagles (-7) vs. Jacksonville Jaguars

  • Date: Sunday, Oct. 2
  • Start time: 1 p.m. ET

Are the Eagles the best team in the NFC? If you look at their schedule, it’s now easy to see how this squad can win 12+ games and perhaps 14+ if they can take one in Arizona or Indianapolis.

Many believed A.J. Brown would be the difference-maker this year, and in many ways he has been, but not always directly. His presence has opened up space for DeVonta Smith. With Jalen Hurts connecting on more than two-thirds of his pass attempts, this is one of the league’s most complete teams.

Meanwhile, Jacksonville’s coming off a huge road win over the Chargers. But with Justin Herbert hobbled and Austin Ekeler struggling, it’s hard to know if the Jags are the real deal at 2-1. Christian Kirk clearly was worth every penny, and their young backfield is gelling. However, they’ve faced three immobile QBs in a row. Sunday will require their defense to play at an entirely different level.

Against-the-spread prediction: Eagles
Moneyline winner: Eagles

Baltimore Ravens (+3) vs. Buffalo Bills

  • Date: Sunday, Oct. 2
  • Start time: 1 p.m. ET

Two teams vanquished by the Dolphins will face off to see who will unexpectedly drop to 2-2. The key here is Buffalo’s banged-up defense. It might be argued that the Bills might have persevered Sunday if not for Josh Allen’s lost fumble on his own 6-yard line in the first quarter, which Miami converted into a touchdown four plays later.

Regardless, both the Ravens and Bills can score in buckets. This one could come down to whichever team has the ball last. As J.K. Dobbins continues this slow return to live action, Buffalo holds several key advantages in the running and passing games — including more than a half-dozen capable receivers, making it incredibly difficult for Baltimore to keep them in check.

Against-the-spread prediction: Bills
Moneyline winner: Bills

Houston Texans (+6) vs. Los Angeles Chargers

  • Date: Sunday, Oct. 2
  • Start time: 1 p.m. ET

The Chargers are in trouble at 1-2 and with their franchise QB playing at less than 100%. Just as importantly, Ekeler is averaging a mere 2.5 yards per carry, which is two full yards off his career average. After scoring 20 times last year, Ekeler’s scoreless through three games.

The question is whether Houston can stop anyone. While their defense might look pretty good on paper (yielding the 13th-fewest points per game), their three opponents have been a mess offensively. The Colts, Broncos, and Bears are hardly a good test of the Texans’ defensive prowess. Even at less than 100%, the Chargers should prove to be their toughest test.

Against-the-spread prediction: Texans
Moneyline winner: Chargers

Pittsburgh Steelers (-3.5) vs. New York Jets

  • Date: Sunday, Oct. 2
  • Start time: 1 p.m. ET

I keep asking this each week: how much longer will Mitch Trubisky be under center? The answer probably is “not much longer,” as their next four opponents will be the Bills, Bucs, Dolphins, and Eagles. Oh, and three of those will be on the road. I predict head coach Mike Tomlin will replace his starting QB during the Week 9 bye.

Of course, it’s not all Trubisky’s fault. Najee Harris (3.2 yards per carry) has regressed behind a porous offensive line — the same line Jaylen Warren has run through quite well (4.7 ypc). This has to be a get-right game for Pittsburgh. Otherwise, for all intents and purposes, their postseason hopes will be dashed.

As for New York, Zach Wilson will make his triumphant return (or at least “a return”) on Sunday. The Jets are similar to the Steelers, in that one “very good” QB could put them on another level. Hopefully, Wilson will be that QB. But one key difference: the Jets’ running game is light years more effective on the ground and through the air. The problem is that Wilson might not be at his best in his first game since last season.

Against-the-spread prediction: Steelers
Moneyline winner: Steelers

Atlanta Falcons (+2.5) vs. Cleveland Browns

  • Date: Sunday, Oct. 2
  • Start time: 1 p.m. ET

A fascinating game featuring two teams on the upswing, albeit a very gradual upswing. Cleveland’s capitalized on a relatively weak September schedule, as well as true No. 1 receiver Amari Cooper and one of the league’s top backfield tandems. Nick Chubb is the guy I thought he’d be last season: a high-volume, highly efficient scoring machine.

The Falcons are coming off a near-miracle comeback against the Rams, followed by a solid road win in Seattle. Their offense rests largely on four players: Marcus Mariota, Cordarrelle Patterson, Drake London, and Kyle Pitts. If Chubb and Kareem Hunt are cooking, it will be tough for Atlanta to keep up unless Mariota takes his game to another level.

Against-the-spread prediction: Browns
Moneyline winner: Browns

Indianapolis Colts (-3) vs. Tennessee Titans

  • Date: Sunday, Oct. 2
  • Start time: 1 p.m. ET

What a victory for the Colts, who are now one win away from potentially moving into first place in the AFC South. Not bad for a team on the cusp of dropping to 0-2-1. Alec Pierce continues to be a name to watch. I pushed the rookie as one of my favorite non-top-50 WRs this summer, and a Week 1 concussion delayed his inevitable breakout. A confident Colts unit with a bolstered receiving corps can win this division.

For Tennessee, Derrick Henry and Robert Woods finally got going, although it was against the 0-3 Raiders. Indy presents a unique challenge for a team that has little room for error. If Henry has trouble moving the ball, Ryan Tannehill doesn’t have the personnel to dominate or even “sort of” thrive.

Against-the-spread prediction: Colts
Moneyline winner: Colts

Detroit Lions (-6) vs. Seattle Seahawks

  • Date: Sunday, Oct. 2
  • Start time: 1 p.m. ET

A battle between two teams with overachieving offenses and relatively weak defenses. The Lions’ breakout hasn’t surprised me, but Seattle’s Week 1 victory certainly did. I pegged the Seahawks as a roughly three-win team. And actually, Geno Smith has been merely adequate while trying to feed two top-20-caliber receivers. A so-so running game led by Rashaad Penny hasn’t helped, though Kenneth Walker III brings a needed extra layer.

I like the Lions winning this one by at least one score. For all his shortcomings, Jared Goff seems to have the personnel and scheme to maximize his talents. The team is No. 2 in the league in points. Even with D’Andre Swift ailing, Jamaal Williams has proven he can lead the backfield. This is a fairly complete offense that should overwhelm the Seahawks.

Against-the-spread prediction: Lions
Moneyline winner: Lions

New York Giants (-2.5) vs. Chicago Bears

  • Date: Sunday, Oct. 2
  • Start time: 1 p.m. ET

After a disastrous 2021 season, conventional wisdom stated that Daniel Jones and Saquon Barkley would be gone after the 2022 campaign, while Kenny Golladay and Kadarius Toney would form a long-term nucleus of a budding passing attack.

How times have changed. With a resurgent Barkley playing for another contract (presumably elsewhere), Jones using his legs more than ever, and Richie James somehow stepping up, the Giants and their new coaching staff are exceeding basement-level expectations in unexpected ways. Losing Sterling Shepard for the season hurts. And yet, they’re facing an ideal matchup while mending their wounds.

Meanwhile, Justin Fields has completed no more than eight pass attempts in each of his three contests this season, while Darnell Mooney and Cole Kmet are largely afterthoughts. David Montgomery’s knee/ankle injuries could be addition by subtraction, assuming Khalil Herbert maintains the dynamism he’s shown since breaking onto the scene last year. Still, this remains a mostly one-dimensional offense.

Against-the-spread prediction: Giants
Moneyline winner: Giants

Dallas Cowboys (-3) vs. Washington Commanders

  • Date: Sunday, Oct. 2
  • Start time: 1 p.m. ET

Dallas keeps lurching forward, awaiting the return of Dak Prescott and its customary high-powered offense. Concerns with Ezekiel Elliott linger, and it’s anyone’s guess whether Cooper Rush can help propel this team to mediocrity.

Washington is in a slightly different boat, with a resurgent Carson Wentz entrenched at QB, plenty of question marks at RB, and an array of capable receivers who could go off any given week. Interestingly, Antonio Gibson is averaging a dreadful 0.6 yards after contact — a far cry from his 1.9 and 2.0 marks the past two seasons. His reduced effectiveness and usage the past two weeks have coincided with two straight losses.

Against-the-spread prediction: Cowboys
Moneyline winner: Cowboys

Carolina Panthers (-1) vs. Arizona Cardinals

  • Date: Sunday, Oct. 2
  • Start time: 4:05 p.m. ET

Baker Mayfield is not the answer. That should be apparent to anyone who’s watched a game or scanned a box score. Notably, his 67-yard TD pass to Laviska Shenault Jr. on Sunday accounted for 12% of Mayfield’s 2022 passing yards — and all 67 yards came after the catch.

While Arizona has its own troubles, they’re more execution-driven than talent-driven. Much like the Broncos, the Cardinals have the pieces in place to be a playoff contender. Last season began with DeAndre Hopkins, Christian Kirk, A.J. Green, and Rondale Moore atop the WR depth chart. So far this season, the team has had to adjust dramatically. They should regain their footing in Week 4.

Against-the-spread prediction: Cardinals
Moneyline winner: Cardinals

Green Bay Packers (-10) vs. New England Patriots

  • Date: Sunday, Oct. 2
  • Start time: 4:25 p.m. ET

A huge betting line suggests backup QB Brian Hoyer will get squashed. There’s not much more to say. While the Packers’ offense lacks the quick-strike ability of past Aaron Rodgers-led teams, it’s still highly potent. And while New England’s defense is good enough to step up, it’s been too inconsistent to trust.

As for the Patriots’ backfield, they’ll keep running Damien Harris and Rhamondre Stevenson (and they will). That might be enough to limit Green Bay’s possessions but not enough to prevail.

Against-the-spread prediction: Patriots
Moneyline winner: Packers

Las Vegas Raiders (-1) vs. Denver Broncos

  • Date: Sunday, Oct. 2
  • Start time: 4:25 p.m. ET

The 0-3 Raiders are in must-win mode. This is not how the franchise drew things up when they acquired Davante Adams. While I urged PFN Pass subscribers to fade Adams in fantasy drafts at his lofty WR4 ADP, I didn’t expect Derek Carr to struggle this much. The yardage and touchdowns are solid. But four interceptions in the face of three very close losses are tough to swallow.

Not that Denver’s playing any better. I missed the mark with them, believing Russell Wilson would be the key to an electric offense not seen in this city since 2014. Instead, Wilson has struggled and the team has left dozens of points on the board near the goal line. Until they turn things around, I’m picking the franchise with its back against the wall.

Against-the-spread prediction: Raiders
Moneyline winner: Raiders

Tampa Bay Buccaneers (+3) vs. Kansas City Chiefs

  • Date: Sunday, Oct. 2
  • Start time: 8:30 p.m. ET

A fascinating matchup made even more compelling by each team’s surprising Week 3 loss — the Bucs at home to the Packers, and the Chiefs versus the seemingly anemic Colts. On Sunday, much hinges on the health of Tom Brady’s elite company of receivers, although a returning Mike Evans obviously will pay huge dividends.

Meanwhile, the Chiefs are headed toward an interesting crossroads if they lose this one, as it would significantly open up the AFC West. Patrick Mahomes and his backfield struggled against Indy. Tampa Bay’s defense won’t be any easier.

Against-the-spread prediction: Buccaneers
Moneyline winner: Buccaneers

San Francisco 49ers (-2.5) vs. Los Angeles Rams

  • Date: Monday, Oct. 3
  • Start time: 8:15 p.m. ET

We are reminded, yet again, that Jimmy Garoppolo is a glorified game manager. When the Niners are clicking on the ground, through the air, and on defense, he’s a fantastic piece of this puzzle. But when a game manager throws a late-game pick to essentially seal the loss, as well as takes four sacks, then there’s little room to recover.

Although Matthew Stafford has struggled, the Rams should be favorites in this one. We haven’t yet seen the best from their defense, and their running game is just starting to function as a top-16 NFL backfield. The defending Super Bowl champs are ramping up, while the 49ers are at risk of stalling.

Against-the-spread prediction: Rams
Moneyline winner:  Rams

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