NFL best bets today: Week 3 picks include Cowboys vs. Bears play [9/21/2025]

Today’s NFL picks for September 21, 2025 are here, with Sunday’s NFL best bets fueled by thousands of predictive simulations analyzing the latest odds and matchups.

These NFL best bets include matchups like the Cowboys vs. Bears game at 4:25PM ET, with this article updated throughout the day to feature the highest-probability plays based on thousands of data-driven simulations from our predictive analytics model.

But if you're serious about long-term profit, it's not just about probability—it's about edge. To unlock our highest-edge NFL bets—the ones with true long-term value—join Dimers Pro.

Pro members get unlimited access to everything Dimers has to offer on Sunday, September 21, 2025, including our full suite of picks and best bets for today and the week ahead.

List of NFL best bets today [9/21, updated 4:02PM ET]

After crunching the numbers and running thousands of simulations, our leading predictive analytics model has identified the best football bets for Sunday, September 21, 2025.

Cowboys ML (-124)

• Probability: 58.6%
• Edge: 3.2%
• Matchup: Cowboys vs. Bears (4:25PM ET, Sunday)

Our model has pinpointed a high-probability NFL betting opportunity today, which comes in the Cowboys vs. Bears matchup. We recommend a bet on the Cowboys ML at -124 odds, with our analysis showing a 58.6% chance of hitting and a compelling edge of 3.2%.

Cowboys vs. Bears under 50.5 points (-110)

• Probability: 55.2%
• Edge: 2.8%
• Matchup: Cowboys vs. Bears (4:25PM ET, Sunday)

Our model has found another strong NFL bet for Sunday's sports action, again in the matchup between the Cowboys and Bears. We suggest placing an over/under wager on under 50.5 points at -110 odds, with a 55.2% probability delivering a 2.8% edge.

Saints +7 (-105)

• Probability: 54.2%
• Edge: 3.0%
• Matchup: Saints vs. Seahawks (4:05PM ET, Sunday)

Our model has found another strong NFL bet for today's football action, this time in the Saints vs. Seahawks game. We recommend a spread bet on Saints +7 at -105 odds. Our projections shows a 54.2% probability and 3.0% edge for this wager.

NFL best bets: Sunday, 9/21/2025

As of 4:02PM ET, here are our top three NFL bets by probability recommended by our model:

Matchup	Bet	Odds	Probability	Edge
Cowboys vs. Bears	Cowboys ML	-124 @ FanDuel	58.6%	3.2%
Cowboys vs. Bears	Under 50.5 Points	-110 @ DraftKings	55.2%	2.8%
Saints vs. Seahawks	Saints +7	-105 @ BetMGM	54.2%	3.0%

The bets listed here are sorted by win probability—but the real path to profit lies in high-edge plays. Dimers Pro unlocks instant access to the most valuable bets across all sports, powered by our advanced predictive model.

Among today's NFL picks is a +245 moneyline bet with a 4.0% edge—the kind of high-upside play that makes a difference over time.

Join Dimers Pro now to access these picks, as well as a comprehensive range of props, trends and parlays for September 21, 2025.

List of upcoming NFL games to bet on [9/21/2025]

• Broncos vs. Chargers (4:05PM ET, Sunday)
• Saints vs. Seahawks (4:05PM ET, Sunday)
• Cardinals vs. 49ers (4:25PM ET, Sunday)
• Cowboys vs. Bears (4:25PM ET, Sunday)
• Chiefs vs. Giants (8:20PM ET, Sunday)

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More about NFL

The bets on this page form part of our NFL player props and NFL best bets series.

For more NFL betting content, we have NFL trends for every game, as well as daily NFL betting news and the latest Super Bowl odds and predictions.

Conclusion

Our NFL best bets are locked and loaded for September 21, 2025, featuring plays such as Cowboys ML and under 50.5 points also in the Cowboys vs. Bears matchup. Powered by advanced simulations, these picks are here to boost your betting game.

This article, enhanced by AI and automation, aims to deliver accurate NFL insights quickly, with human oversight ensuring high editorial quality. Our predictions are grounded in current data to help you make informed decisions. For additional resources and advice on responsible gambling, please call 1-800-GAMBLER.

All odds and probabilities in this article are correct and accurate at the time of publication.

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