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NFL Betting Predictions: Week 4 Opening Line Report and Picks

by Spencer Toth - 9/23/2025

NFL betting predictions Week 4 opening line report Trevor Lawrence Jacksonville

One of the best strategies for winning in the NFL is to take advantage of line movement. The closing lines in the NFL are often very sharp, but the early lines can leave money to be made against the spread. While an extra point, or even half a point, can feel insignificant, it can be the difference between winning and losing in the long run. Our Week 3 opening line picks featured the perfect example. The Los Angeles Chargers were -2.5 point favorites early in the week, before closing at -3. They went on to win by exactly three points, allowing us to chalk up a win while a closing line selection would have resulted in a push. We also correctly picked the Chiefs at -5.5, but fell short on the Packers -7.5 after Green Bay lost outright. Before we get into the Week 4 picks, here are the biggest storylines from a season-defining Week 3 slate.

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  • Isaiah Rodgers, Take a Bow: Isaiah Rodgers had the defensive performance of a lifetime in the Vikings' 48-10 beatdown against the Bengals. He forced two fumbles, one of which he returned for a touchdown, and recorded a pick-six. He was the first player to do so since stats have been tracked in 1991, and was likely the only player in NFL history to achieve this feat. 
  • Daniel Jones for MVP? The Indianapolis Colts finally punted the football in Week 3, but still put up 41 points on the Tennessee Titans. It would be an understatement to say that Daniel Jones is settling in nicely with the 3-0 Colts. 
  • No Daniels? No Problem. Washington was able to bounce back nicely from their embarrassing defeat against Green Bay in Week 2. Marcus Mariota led the Washington offense to 41 points and a comfortable victory. 
  • Eagles find a way: Philadelphia overcame a late deficit to stay undefeated in Week 3. A pair of blocked field goals in the fourth quarter will not be how they expected to get it done, but every victory is worth the same. 
  • Upset in Cleveland. The Green Bay Packers were the second-biggest favorites of Week 3, but lost outright to the lowly Cleveland Browns. A lifeless offense managed just 10 points, while the Browns scored 13 unanswered fourth-quarter points. 
  • Chiefs get on the board: The Kansas City Chiefs avoided an 0-3 hole with a comfortable win over the Giants on Sunday Night Football. The reigning AFC champions still have a lot of work to make the playoffs, especially with the Ravens looming in Week 4. 
  • Lions are roaring: There was reason for concern after the Lions crumbled in Week 1, but they have responded with 90 points across their two recent victories. A third straight Derrick Henry fumble helped them along the way, but Detroit was the better team for the majority of their Monday Night affair. 

There are three Week 4 lines that must be scooped up immediately. As we saw with the Chargers last week, even an extra half point in your favor can be the difference between winning and losing in the NFL over the course of an entire season. 

Game 1: Los Angeles Chargers at New York Giants

Opening Line: Los Angeles Chargers (-6)

This line opened up at -5.5 in favor of the Chargers, but quickly jumped to 6 points and could be going even higher. While Los Angeles still has their flaws, this is a well-built football team with a truly elite quarterback. Justin Herbert made several difficult throws to secure a victory against the Broncos last week and will do so again in New York. Herbert’s combination of accuracy down the field with his mobility in a collapsing pocket makes him impossible to slow down. The Giants' pass rush is impressive on paper, but the Chargers have invested in keeping Herbert upright, and we can trust their offensive line to do its job. For the Giants' offense, things could not be more bleak. A 37-point explosion against a poor Dallas defense bought Russell Wilson more time as the starter, but a pair of single-digit showings otherwise has not helped his case. It is only a matter of time before Jaxson Dart comes into this offense, and the Giants have already given up on any faint playoff aspirations. This could be the final start of Wilson’s historic career, and that is rarely a good sign against a top contender like the Chargers. This spread could easily climb up to a touchdown before kickoff, and locking in -6 is the way to go. 

Pick: Los Angeles Chargers (-6)

Game 2: Washington Commanders at Atlanta Falcons

Opening Line: Washington Commanders (-2.5)

The status of Jayden Daniels has not yet been confirmed for this game, but this is a favorable line even if he is forced to sit out. Marcus Mariota proved he can lead this Washington offense, and it won’t take much to beat the Falcons at this stage of the season. Atlanta has looked dreadful on both sides of the ball, and it is shocking to see a line under a field goal in this matchup. Michael Penix Jr. has consistently made poor decisions in the pocket, and the Falcons can’t expect 100+ yards from Bijan Robinson on a weekly basis. A line like this, given the current Washington quarterback situation, is exactly what we are looking for early in the week. The -2.5 point spread is under the key number of 3 (nearly 20% of NFL games finish with a three-point margin of victory). Additionally, if Jayden Daniels is in for Washington, this line will skyrocket, while it shouldn’t move much if he is forced to stay on the sidelines. Even if it does drop a point or two, a closing spread of -1 or -1.5 is far less impactful compared to this line bumping up to -3.5 or higher. These are two teams heading in completely different directions, and laying the points with Washington is the top play of the week. 

Game 3: Jacksonville Jaguars at San Francisco 49ers

Opening Line: San Francisco 49ers (-3.5)

Brock Purdy will likely be back in the lineup for the undefeated 49ers, but that doesn’t mean we should be running to the window to lay these points. San Francisco still has a lengthy list of injuries to deal with heading into their matchup against Jacksonville. Nick Bosa suffered a season-ending injury last week, and they are still missing multiple skill position players. Meanwhile, Jacksonville improved to 2-1 last week and was very close to getting off to a 3-0 start. Trevor Lawrence has been able to spread the ball for the Jags, and this is all while WR1 Brian Thomas Jr. has been largely ineffective. The Jaguars' defense is just as strong, and this is a team to watch in the AFC South this season. A point spread above three points doesn’t accurately reflect where these two teams stand right now, and we will grab the field goal plus the hook in a game that should go down to the wire. 

Pick: Jacksonville Jaguars (+3.5)

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