NFL Week 5 Predictions: 3 Best Bets and Picks for Sunday

NFL Week 5 Best Bets in Summary

• Colts +2.5 (-110)
• 49ers +3.0 (-110)
• Lions -5.5 (-104)

Week 5's Sunday slate gives us plenty to dig into, with divisional showdowns, several short spreads, and a heavyweight NFC West matchup between the San Francisco 49ers and Seattle Seahawks.

Seattle enters Sunday as a home favorite versus San Francisco while the Indianapolis Colts are catching points in a matchup where our numbers give them a strong chance to win outright. Later in the afternoon, Detroit gets an opportunity to bounce back against a struggling Arizona defense.

Here are three of our favorite NFL bets for Sunday's Week 5 slate.

All NFL odds come from FanDuel Sportsbook's NFL betting odds and may change after this article is published.

NFL Picks and Predictions for Week 5

Colts +2.5 (-110)

Colts vs. Steelers (1 p.m. ET)

The market has the Pittsburgh Steelers favored at home, but numberFire gives the Indianapolis Colts a 56.4% probability of winning the game outright. That disconnect makes grabbing the points an enticing option.

Indianapolis has won two straight after an 0-2 start, and Jonathan Taylor gives the Colts a clear path to controlling this matchup. Taylor has handled 86 carries for 353 rushing yards and 6 touchdowns through four games, including 20 carries for 95 yards and a pair of scores in last week's win over the Washington Commanders.

The offense hasn't been overly dependent on Daniel Jones having to create big plays through the air, which is useful against a Pittsburgh defense that can generate pressure.

There's certainly some risk with Indy's offense, but I don't see much separating these teams. The Steelers are coming off a loss to the Cleveland Browns while Indianapolis has covered the spread in three of its first four games.

While numberFire favors Indianapolis outright, I'll take the points instead of backing Indy to win.

49ers +3.0 (-110)

49ers vs. Seahawks (4:25 p.m. ET)

The San Francisco 49ers enter Week 5 at 4-0, and their start has been backed up by some excellent underlying numbers. San Francisco ranks first in the NFL in EPA per play while generating a 53.1% offensive success rate through four games. Defensively, the Niners have permitted an explosive play on only 2.7% of snaps, the lowest rate in football.

Obviously, the Seattle Seahawks deserve plenty of respect. The Seahawks are 3-1, have allowed only 18.3 points per game, and have surrendered just 4.0 yards per play. They're also holding opposing passing attacks to 4.3 net yards per attempt.

That's why I don't necessarily want to pick a San Francisco outright win. Seattle's defense is good enough to make life difficult on Brock Purdyand company, particularly at Lumen Field. But getting a full three points with an undefeated team that has played at an elite level on both sides of the ball is appealing.

San Francisco does have some noteworthy injuries, per usual, with Nick Bosa and Kyle Juszczyk expected to miss the game. Still, the 49ers have covered in three of four games, and I think this matchup is close enough that taking the Niners +3.0 is how I’m approaching it.

Lions -5.5 (-104)

Lions vs. Cardinals (4:25 p.m. ET)

The Detroit Lions‘ defense is a concern, but this is a matchup where the offense should be able to do enough damage for the Lions to win comfortably.

The Lions are averaging 29.8 points and 389.3 total yards per game through four weeks, which ranks fifth and sixth in the NFL, respectively. Their offense has topped 30 points in three of its four outings.

The Arizona Cardinals haven't shown much ability to slow opponents lately.

The Cardinals have surrendered more than 30 points in three consecutive games, and their defense has really struggled in pass coverage and generating pressure. That's a dangerous combination against a Detroit offense capable of attacking defenses in multiple ways.

Amon-Ra St. Brown gives Jared Goff an elite target in the middle of the field while Jahmyr Gibbs helps Detroit stress defenses both as a runner and receiver.

The concern is Detroit's own defense. The Lions rank 31st in points allowed and dead last in defensive EPA per play, so Arizona has a realistic path to putting some points on the board, too. But if it turns into a shootout, I trust Detroit’s offense more — even on the road.

NFL Betting FAQ

How does the point spread work in NFL betting?

The point spread gives the underdog a specified number of points and subtracts that same number from the favorite. For example, if a team is favored by 3.5 points, it must win by at least 4 points for a bet on that team to cash. A bet on the 3.5-point underdog would win if that team wins outright or loses by 3 points or fewer.

What is an NFL moneyline bet?

A moneyline bet is a wager on which team will win the game outright. The point spread does not matter. Favorites typically have negative moneyline odds, while underdogs usually have positive odds.

What is an over/under in NFL betting?

An over/under, also known as a game total, is a wager on the combined number of points scored by both teams. If the total is set at 47.5, an over bet wins if the teams combine for at least 48 points, while an under bet cashes if they score 47 points or fewer.

What are NFL player prop bets?

NFL player props are wagers based on an individual player's performance rather than the final result of the game. Common markets include passing yards, rushing yards, receiving yards, receptions, passing touchdowns, and anytime touchdown scorers.

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Which bets stand out to you this week? Check out FanDuel Sportsbook's latest NFL odds to see the full menu of options. You can also check out our How to Bet on the NFL guide.

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The above author is a FanDuel employee and is not eligible to compete in public daily fantasy contests or place sports betting wagers on FanDuel. The advice provided by the author does not necessarily represent the views of FanDuel. Taking the author's advice will not guarantee a successful outcome. You should use your own judgment when participating in daily fantasy contests or placing sports wagers.