The 2025 NFL season kicks off with two headline matchups, and we’ve narrowed down the best picks and parlays to consider. For Thursday night’s rivalry clash, our top betting suggestion is the Eagles moneyline against the Cowboys. On Friday, in Brazil, the Chiefs spread at -5.5 looks like the strongest play against the Chargers.
In this article, you’ll find our main recommendations plus alternative options for higher odds. We’ll cover the Cowboys vs. Eagles and Chiefs vs. Chargers, breaking down team form, roster changes, and head-to-head records. Keep in mind: betting is always unpredictable, and these are suggestions based on available data as of September 4, 2025.
During the preseason, our picks and predictions achieved an 80% success rate.
Dallas Cowboys vs. Philadelphia Eagles – Home Edge Favors the Defending Champs
The Eagles come in as the reigning Super Bowl champions, with Jalen Hurts and A.J. Brown leading one of the league’s most explosive offenses. The addition of Saquon Barkley only adds to their firepower. Playing at home in a rivalry opener, they have both form and momentum on their side.
For the Cowboys, Dak Prescott’s performance will be key, especially after the team traded away Micah Parsons, leaving their defense exposed. Their preseason was inconsistent, with only one win. Considering the matchup and home advantage, the Eagles moneyline is the safer bet. For a higher-risk option, the Over 48.5 looks appealing given both teams’ offensive potential.
Kansas City Chiefs vs. Los Angeles Chargers – Mahomes & Kelce Lead the Way in Brazil
The Chiefs start their season in Brazil, carrying the momentum of a 15–2 record and another Super Bowl title. Patrick Mahomes and Travis Kelce remain one of the NFL’s most reliable duos. Despite a winless preseason, Kansas City tends to flip the switch once the games matter.
The Chargers, meanwhile, are under new leadership and adjusting to a fresh system. With Justin Herbert still a major threat but fewer proven weapons, they may need time to settle in. The Chiefs -5.5 spread is the recommended play here, backed by their dominance in recent head-to-head meetings. If you’re chasing higher odds, consider the Over 51.5, as both quarterbacks are capable of turning this into a shootout.
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- Source: https://sportshandle.com/best-picks-and-parlays-for-nfl-season-opening/