Buffalo Bills (vs. New Orleans Saints)
The Buffalo Bills are now 3-0 on the season and have been on some extended rest, as they played on Thursday Night Football in Week 3 and beat up on the Miami Dolphins. Well, the New Orleans Saints come to town, and the Saints have truly been the worst team in football thus far.
The Saints just got brutalized by the Seattle Seahawks and really don't have much going for them in the 2025 NFL Season. However, New Orleans can be good enough to play spoiler from time to time, and with the Bills coming into this game as a massive favorite, it only makes sense that Buffalo has a letdown.
From time to time, the Bills get in their own way and lose a game they absolutely should have won. It's been a theme in the Josh Allen/Sean McDermott era, and it could come to bite them here in Week 4. The Saints really have nothing to lose at this point and will find a way to beat the Bills in their house.
Prediction: Saints win 21-20
Los Angeles Chargers (@ New York Giants)
The final team on upset alert in Week 4 is the Los Angeles Chargers, who are traveling across the country for a 1:00 PM, east coast game against the New York Giants. Teams traveling east for the early window on Sundays can have massive letdowns.
And through three weeks, the LA Chargers have done anything but letdown. LA is now 3-0 in the division and clearly in the driver's seat, but this offensive line is definitely on the struggle bus, as the Broncos' pass rush got home a ton in Week 3.
The New York Giants should be able to hit Justin Herbert early and often, and if the G-Men bench Russell Wilson for Jaxson Dart, the potential momentum of a rookie QB making his first start in the NFL could be enough for the Chargers to drop their first game of the season.
It would be an unlikely outcome, but that is the point here with our upset picks for Week 4. The Los Angeles Chargers are a very good football team, but they'll lose their first game of the season in a shocking result.