NFL Week 4 Best Bets – Predictions & Picks for NFL Week 4

Last Updated: Oct 1, 2021

Week 3 of the NFL season was another profitable one for us with our best bets. We went 4-2 total, bringing our overall record up to 14-4.

Week 4 promises to be another great week with several fascinating contests and matchups. To prepare you for the week ahead, here are our best bets for Week 4 in our NFL prediction and picks series. All odds are current as of Monday, September 27.

Marcus Mosher’s Best Bets NFL Betting Record: 14-4

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Read Chris Wassel’s Caesars Sportsbook review for more insight and get your welcome bonus below, or continue reading this analysis for our Week 4 tipster picks.

NFL Week 4 Best Bets

Seattle Seahawks vs San Francisco 49ers

One of the best rivalries in the NFL over the last decade has been between the Seattle Seahawks and San Francisco 49ers. These NFC West foes have played in multiple thrillers that have literally come down to the final play and sometimes the final yard.

Both teams are coming off rough Week 3 losses and need wins to keep pace with the Los Angeles Rams and the Arizona Cardinals in the division, both of whom remain undefeated. Seattle in particular will be looking to bounce back from a 1-2 start, so expect Russell Wilson to play with more urgency and find a way to win this huge game in Week 4.

Seahawks vs 49ers Prediction: Seahawks 24, 49ers 21

Seahawks vs 49ers Best Bet: Seahawks +3 (-110) at BetMGM

The Seahawks have had a ton of success against the 49ers recently, winning 13 of their last 15 meetings. And with Seattle having the better quarterback in this game, it’s tough to pick against them on the point spread.

This is likely a game that comes down to the final possession, so getting a three-point advantage is huge here. Betting the Seahawks to win the game outright isn’t a bad call either.

Seahawks vs 49ers Best Bet: Under 52 (-110) at BetMGM

Divisional matchups tend to be lower-scoring, and that is especially true when it comes to Seattle and San Francisco. Both teams will want to establish the run and lean on their defenses to win this game.

The Under is the safe bet here, as both sides could struggle to score more than 24 points. Be sure to shop around our NFL gameday odds for the best price, as the total varies depending on the site.

Russell Wilson Seattle Seahawks QB

Russell Wilson’s Seattle Seahawks will try to even their record at 2-2 with a Week 4 win over the San Francisco 49ers. (Image: USA TODAY Sports)

Kansas City Chiefs vs Philadelphia Eagles

For the first time in the Patrick Mahomes era, the Kansas City Chiefs have a losing record. They now sit at 1-2 after back-to-back losses to the Baltimore Ravens and Los Angeles Chargers. Can they bounce back on the road and beat the Philadelphia Eagles in Week 4?

Kansas City is the far better team and could easily be 3-0 if a couple of breaks had gone their way. Philadelphia is talented enough to hang around for a while in this game, but the Chiefs should win by multiple scores. Look for Mahomes to throw for well over 300 yards and multiple touchdowns in a Week 4 victory.

Chiefs vs Eagles Prediction: Chiefs 34, Eagles 21

Chiefs vs Eagles Best Bet: Chiefs -6 (-110) at BetMGM

After back-to-back losses, the Chiefs feel destined to rebound in a big way in Week 4 against the Eagles, who are coming off a road Monday Night Football game in Dallas. This appears to be a good spot for Kansas City, as Philadelphia can be exposed in the secondary.

Look for the Chiefs to try to make a statement in this game, as they should easily score 30 or more points in Week 4. Kansas City feels like a lock to win this contest by double digits, making this my NFL bet of the day.

Chiefs vs Eagles Best Bet: Over 54.5 (-110) at BetMGM

This game is tied with the Rams vs Cardinals contest for the highest point total of the week. However, bettors shouldn’t be afraid to take the Over here, as neither defense is likely to slow the game down too much. Instead, look for both teams to move the ball up and down the field as they create chunk plays in the passing game, resulting in plenty of points.

Tampa Bay Buccaneers vs New England Patriots

Tom Brady and Rob Gronkowski will finally face their former team for the first time in this hotly-anticipated Sunday Night Football showdown in Foxborough.

With Tampa Bay coming off their first loss since last November, you know they’re going to be extra motivated to get back in the win column, especially against Bill Belichick‘s New England Patriots. New England’s offense has struggled with rookie Mac Jones under center, looking vanilla and lacking explosive plays.

This is a meeting between the defending Super Bowl champions and a team that’s in the middle of a rebuild. While the storyline is juicy, don’t expect the game itself to be very competitive. Tampa Bay should win this game by multiple touchdowns in Week 4.

Buccaneers vs Patriots Prediction: Buccaneers 31, Patriots 10

Buccaneers vs Patriots Best Bet: Buccaneers -6.5 (-110) at BetMGM

Despite their Week 3 loss, the Buccaneers are still one of the best teams in football, while the Patriots look like an average team at best. Brady is going to want to put on a show against his former team and will likely throw multiple touchdowns, several of which could end up in the hands of Gronkowski.

While Tampa Bay will be playing on the road, Brady is plenty comfortable in Foxborough. He also has far more weapons at his disposal than Jones does, and it wouldn’t be a surprise if the game is over by halftime in this potential blowout.

Buccaneers vs Patriots Best Bet: Under 49 points (-115) at BetMGM

Tampa Bay’s defense was shredded in Week 3 by Matthew Stafford and the high-powered Rams, but they will have a much easier task in Week 4. New England is averaging just 20 points per game in the post-Brady era and has scored only four total touchdowns in three games this season.

The Patriots’ offense will likely continue to struggle against the Buccaneers’ defense, which appears poised to feast on Jones after he threw three interceptions in Week 3. Meanwhile, New England’s stout defense will do its best to keep Brady in check, making the Under a smart play here.

Thanks for reading our NFL Week 4 Best Bets! For more NFL Week 4 betting tips, check out our NFL Week 4 Parlays Picks & Predictions.


Marcus Mosher

Marcus Mosher is an NFL analyst at The Game Day, residing in Erie, PA. He covers the NFL from a betting and fantasy perspective, producing written and video content. Marcus currently hosts multiple football-related podcasts and is a managing editor at USA Today’s Sports Media Group covering the Las Vegas Raiders. He has previously worked at The Athletic and Bleacher Report.

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