Early NFL Week 5 Predictions and Picks Against the Spread: Fallout From Injuries to Jonathan Taylor, Javonte Williams, and Cordarrelle Patterson

If you're betting on 2022 NFL games -- whether props, DFS, point spreads, or moneylines -- here are our early NFL Week 5 predictions and picks.

Hello, everybody. Here’s an early look at our NFL Week 5 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 5 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.

Denver Broncos (-3) vs. Indianapolis Colts

  • Date: Thursday, Oct. 6
  • Start time: 8:15 p.m. ET

As of early Monday morning, Jonathan Taylor appears to be questionable for Thursday’s game. There are no adequate replacements for one of the best RBs in the game. The underutilized Nyheim Hines doesn’t profile as a bell cow, and third-stringer Deon Jackson has 15 career rushes for 28 yards. The thought of Matt Ryan “carrying” the Colts to victory is like Tom Brady carrying his kid’s books to school.

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As much as Denver has struggled on offense, they’ll have an advantage over Indy if Taylor sits. Yes, the strong possibility of losing Javonte Williams for an extended period would be crushing. But they still have Melvin Gordon III and the intriguing Mike Boone. Russell Wilson has also actually been looking a little more like his old self. Not quite. But getting there.

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

Green Bay Packers (-7.5) vs. New York Giants

  • Date: Sunday, Oct. 9
  • Start time: 1 p.m. ET

What do you get when a team has Saquon Barkley and other players? A team that probably won’t keep Barkley after this season. In fairness, the Giants have a lot of good players. But their receiving corps needs more help than any one or even two injured WRs can offer. This is as one-dimensional an offense as any in football. Ironically, Barkley looked like damaged goods after last season. Now he once again looks like a franchise RB. Too bad his team hasn’t caught up.

The Packers gutted out their victory over the Patriots. This weekend shouldn’t be as tough. Of course, who knows. But Green Bay’s backfield should control the line of scrimmage, and the ascending Romeo Doubs (and a healthy Allen Lazard) might be all Aaron Rodgers needs to win games like this one.

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

Buffalo Bills (-14) vs. Pittsburgh Steelers

  • Date: Sunday, Oct. 9
  • Start time: 1 p.m. ET

The betting line looks almost cartoonish, especially when considering Buffalo nearly fell to 2-2 on the season, while Pittsburgh blew a late lead that would have lifted them to 2-2. Instead, we see two teams going in opposite directions, and assuming Kenny Pickett will start the rest of the season, there will be some growing pains. His first career start on the road against one of the league’s top defenses (despite its injuries) will test him more than he deserves to be tested at this early stage.

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

Cleveland Browns (+3) vs. Los Angeles Chargers

  • Date: Sunday, Oct. 9
  • Start time: 1 p.m. ET

Can any team stop Nick Chubb? It’s a fair question for an in-his-prime running back who’s pushing Jamaal Charles for the NFL’s highest career yards per carry (minimum 750 carries).

Still, the Browns are giving up too many points given their limitations in the passing game, and the opposing Chargers can score in buckets — and are getting healthier. Cleveland will need to execute almost flawlessly to keep pace with LA’s high-ceiling passing and running games. I don’t see it happening.

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

Minnesota Vikings (-7) vs. Chicago Bears

  • Date: Sunday, Oct. 9
  • Start time: 1 p.m. ET

Justin Fields is coming off a 174-yard passing performance against the Giants, adding 52 on the ground. He didn’t find the end zone and was sacked six times. Yet, it might have been his best effort of the season. And that’s a problem heading into a tougher road game against Minnesota. It’s hard to envision Chicago making this one competitive unless Fields takes his game to another level.

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

New England Patriots (-2.5) vs. Detroit Lions

  • Date: Sunday, Oct. 9
  • Start time: 1 p.m. ET

These are “early” predictions because we don’t yet know how the starting lineups will shake out by Sunday. Who will be New England’s starting quarterback? Perhaps more importantly, will any of Detroit’s top three playmakers (D’Andre Swift, Amon-Ra St. Brown, and/or DJ Chark) return?

At the moment, Detroit’s objectively horrendous defense is the X-factor. The Patriots should find a way to win, thanks to a backfield that should have its way with the Lions’ defensive line.

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

New Orleans Saints (-5) vs. Seattle Seahawks

  • Date: Sunday, Oct. 9
  • Start time: 1 p.m. ET

Again, “early” predictions, because Alvin Kamara and Michael Thomas alone could mean an extra touchdown in this game, and maybe more. Look, the Seahawks are clicking on offense in ways I hadn’t anticipated this summer. After getting cast aside for most of his career, Geno Smith has found a home and made the most of this opportunity. Still, New Orleans’ defense is a far cry from Detroit’s, and the Seahawks should face a lot more obstacles reaching even 17 points on Sunday.

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

New York Jets (+3) vs. Miami Dolphins

  • Date: Sunday, Oct. 9
  • Start time: 1 p.m. ET

Who will be under center for Miami, and will it matter? Teddy Bridgewater certainly can get it done against New York’s up-and-coming squad, thanks to quite possibly the best WR tandem in the league.

The Dolphins’ defense will be the key to this one, as the young Zach Wilson is error-prone. Slowing the Jets’ RBs and forcing Wilson to win it through the air worked against Pittsburgh, but it probably won’t work against Miami.

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

Tampa Bay Buccaneers (-8.5) vs. Atlanta Falcons

  • Date: Sunday, Oct. 9
  • Start time: 1 p.m. ET

When Brady looks human, so do the rest of the Bucs. Consider that, in Week 2, the opposing Saints came up empty four or five times in Tampa Bay territory, mostly off of interceptions and a fumble. If not for that collapse, the Buccaneers might be 1-3 right now. Instead, they’re a struggling 2-2 team that’s finally healthy, but nowhere close to midseason form.

Still, Atlanta represents an ideal matchup for a struggling, proud franchise loaded with talent that the Falcons can only dream of securing. Yes, Drake London and Kyle Pitts are future NFL stars. But the Falcons are probably at least two seasons away from being an above-.500 team. In Week 5, Tampa Bay likely will dominate them on both sides of the ball. It doesn’t help that Cordarrelle Patterson has been placed on injured reserve, pushing rookie Tyler Allgeier into the limelight in a tough matchup.

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

Washington Commanders (+2.5) vs. Tennessee Titans

  • Date: Sunday, Oct. 9
  • Start time: 1 p.m. ET

I didn’t think Tennessee would beat the Colts this past weekend, though it’s fair to say Indy did their part to lose. Still, the Titans lack the passing game to keep pace with high-scoring opponents. Derrick Henry will get his touches and yards, but beyond that, many seem to be waiting for the Malik Willis era to begin.

I believe Washington will take this one, sending the Titans to 2-3 and forcing them to decide whether to become buyers before the trade deadline to add a needed receiver — especially if the Week 4 injury to Treylon Burks proves serious.

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

Jacksonville Jaguars (-7) vs. Houston Texans

  • Date: Sunday, Oct. 9
  • Start time: 1 p.m. ET

Great teams sometimes follow up ugly losses with beautiful wins. While Trevor Lawrence and the Jaguars aren’t yet “great,” through four weeks, they’re far better than most prognosticators anticipated, and they put a scare in the Eagles before things fell apart.

This team is oh so close to breaking through in the wide open AFC South. Despite the Texans’ ascending Dameon Pierce, I see the Jags hanging 30+ on hapless Houston and winning comfortably.

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

Carolina Panthers (+4.5) vs. San Francisco 49ers

  • Date: Sunday, Oct. 9
  • Start time: 4:05 p.m. ET

As longtime readers know, I was down on Baker Mayfield entering his first full season as an NFL starter. He looked closer to Ryan Leaf than to Peyton Manning. As a rookie the year before, most of his best performances came against bottom-of-the-barrel defenses. He struggled against better ones. Not surprising, but also reflective of a larger question: Could Mayfield adjust as defenses adjusted against him?

These days, Mayfield probably would be on the bench if Sam Darnold or Matt Corral were healthy. It would take a monumental shift for the former No. 1 overall draft pick to turn around his career in Carolina. And facing a tough Niners defense won’t help his cause.

Against-the-spread prediction: 49ers
Moneyline winner: 49ers

Los Angeles Rams (-4.5) vs. Dallas Cowboys

  • Date: Sunday, Oct. 9
  • Start time: 4:25 p.m. ET

It would be easy to count out the Rams after what we witnessed Monday night against the 49ers. For the first time since 2016, Matthew Stafford has endured back-to-back zero-TD performances. Things are not looking promising for the defending champions.

And yet, Cooper Kupp remains relatively untested. Impressive given the cards stacked against him? Absolutely. But I’m expecting Los Angeles to return home stronger than how they left it. The running game has nowhere to go but up, and Kupp remains arguably the best non-QB weapon in the sport.

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

Arizona Cardinals (+6) vs. Philadelphia Eagles

  • Date: Sunday, Oct. 9
  • Start time: 4:25 p.m. ET

I’m having a tough time sizing up this contest. On the one hand, Philly looks like the best team in the NFC. On the other hand, Arizona could turn a corner if only their running game hit the next gear. Maybe more Eno Benjamin would help, or perhaps James Conner can rebound.

Regardless, the Eagles should take this one. But by how much? For now, I’m comfortable picking Philadelphia to cover. If their line moves up to eight or more points, I’ll probably switch sides.

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

Baltimore Ravens (-3) vs. Cincinnati Bengals

  • Date: Sunday, Oct. 9
  • Start time: 8:20 p.m. ET

If you like football, this game will have everything. Except defense. Well, maybe that’s not fair. But we’re talking about two teams that can score 40+ when things are clicking.

The betting line suggests this is an even matchup that favors the home squad. I agree with that assessment. This one could go back and forth, with Lamar Jackson — coming off a rough outing against Buffalo — proving once again to be the difference.

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

Kansas City Chiefs (-6.5) vs. Las Vegas Raiders

  • Date: Monday, Oct. 10
  • Start time: 8:15 p.m. ET

After watching Kansas City dismantle Tampa Bay’s supposedly elite defense, I cannot bet against the Chiefs on Monday night. As an analyst, I’m admittedly frustrated with my inability to assess this team. Are they better than they look on bad days, or are they worse than they look on incredible days? Never count out Patrick Mahomes — except he’s human and has been prone to inexplicable struggles.

No doubt, this game should feature a lot of offense, as the desperate 1-3 Raiders try to claw back into postseason contention. I think the Chiefs are simply too tough at too many key positions.

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


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