NFL Betting Predictions: Week 4 Opening Line Report and Best Bets

by Spencer Toth - 9/29/2026

NFL betting predictions Week 4 opening line report Jordan Love

The closing lines against the spread in the NFL are some of the sharpest numbers in the world of sports betting, but we can find value by locking in picks on the opening lines. It may not sound like much, but if we can secure even a point of value compared to the odds at kickoff, that could be the difference between winning and losing in the long run. Last week, we went 0-3 against the spread, but we will get back in the win column in Week 4. The 49ers allowed the Cardinals to get a backdoor cover in the final minute of the fourth, while the Eagles and Saints came out flat against the Bears and Raiders. Before we jump into our Week 4 picks, here are the biggest storylines from around the league in Week 3.

Trouble in Green Bay: The Green Bay Packers got blown out at home by the previously winless Atlanta Falcons, struggling on both sides of the ball. The injuries are piling up, while Jordan Love looks like a shadow of his former self.
Drake ‘Schedule’ Maye: Drake Maye and the Patriots had a historically easy schedule last year en route to the Super Bowl, and this was a real ‘prove it’ year. After their Week 3 35-6 drubbing at the hands of the Jaguars, the Patriots are now in real danger of proving the naysayers right.
Down go the champs: Seattle walked into Washington riding a 12-game win streak dating back to last season, and took on a Commanders side missing Jayden Daniels. However, Washington prevailed in a 33-31 thriller, with Marcus Mariota throwing for three touchdowns. Seattle will rebound as they lost the turnover margin by three, and outgained Washington by nearly 200 yards, but it is a good reminder that on any given Sunday…
Bedlam in Brazil: Dallas and Baltimore put on a show in Rio de Janeiro, with the Ravens ultimately winning 34-31. The Cowboys looked to have sent the game to overtime with a field goal with seven seconds left, but a lightning quick Ravens drive gave Tyler Loop the last laugh with a 56-yard winner.
Time to worry about the Rams? Los Angeles entered the season as the runaway Super Bowl favorites, but a 1-2 start with a pair of troubling losses has knocked them off the throne. They took a 16-0 lead into halftime against the Broncos on Sunday Night Football, but a late Bo Nix touchdown sent the Rams to the bottom of the NFC West.
Case Keenum, take a bow: The Chicago Bears had to turn to Case Keenum to start their Monday night matchup against Philadelphia, and after more than 1,000 days on the sidelines, Keenum looked flawless. The Eagles shot themselves in the foot multiple times, but Keenum was composed, avoiding turnovers, and guided the Bears to a 27-7 win.

Now that Week 3 is behind us, it is time to get into the Week 4 NFL picks. Make sure you lock these ones in immediately as there is no guarantee these prices will be available when kickoff rolls around.

Doc’s Sports offers NFL expert picks for every game on our NFL predictions page.

Game 1: Indianapolis Colts vs Washington Commanders (In London)
Opening Line: Indianapolis Colts (-3.5)

Neither of these teams have looked great to start the season with matching 1-2 records, but both got into the win column last week with massive victories. The Colts leaned on their run game to take down the Texans, while Washington took advantage of Seattle’s mistakes to dethrone the defending champions. They now take a trip across the pond to face off at Tottenham Hotspur Stadium, in what could prove to be a pivotal game for both teams. The Colts have leaned on Jonathan Taylor to find success, and this game will be won or lost based on how Washington can slow down the run. Their revamped defensive line has found a way to make an impact, while an improving secondary will take care of the rest. On the other side of the ball, Marcus Mariota is one of the best backups in the league, plays a similar style to starter Daniels, and has no shortage of capable pass catchers to aim at. The Colts defense stepped up against C.J. Stroud and the Texans, but Houston isn’t a great team offensively, and I can’t buy into that win too heavily. I have this game at a true pick ‘em, and the fact we are getting more than a field goal on the spread makes this the most confident play of the week. I wouldn't be surprised to see this line drop to a flat -3 or even -2.5 before kickoff, which makes locking in this price immediately incredibly crucial.

Pick: Washington Commanders (+3.5)

Game 2: Denver Broncos at San Francisco 49ers

Opening Line: San Francisco 49ers (-2.5)

The 49ers have gotten off to a perfect 3-0 start while the Broncos have ripped off back-to-back wins over the Jaguars and Rams. This will be a high level game of football on both sides of the ball, but that still doesn’t excuse this line. The 49ers have been forced to deal with injuries to start the season, but they have arguably been the most dominant team in the league. They secured two blowouts to start the year and a six-point win over the Cardinals that was a two-score game for most of the contest, and have no plans to slow down now. Brock Purdy has taken a while to finally silence the doubters, and there is no viable reason to expect a sudden falloff. With Christian McCaffrey in the backfield, a talented skill position group led by George Kittle, and an excellent offensive line, the 49ers will be able to move the ball on Sunday afternoon. However, I am feeling less confident in Bo Nix and the Broncos. Their comeback win against the Rams in primetime is fresh in the public’s mind, but they are unlikely to pull off a miraculous win again if they fall asleep for multiple quarters against San Francisco. This is a line I expected to be closer to a touchdown than a field goal with how the 49ers have looked, which makes laying the points the way to go. Securing a crucial -2.5 spread is another benefit, as almost all the value evaporates if this line shifts.

Pick: San Francisco 49ers (-2.5)

Game 3: Detroit Lions at Carolina Panthers

Opening Line: Detroit Lions (-3.5)
The Detroit Lions have eked their way to a 2-1 record to start the year, but it has been far from pretty. They needed overtime to beat the Saints and a last-gasp touchdown to overcome the Jets, with a blowout loss to the Bills sandwiched between those two victories. While they haven’t looked good, this is a great spot to get back on track. The Detroit offense looks like it is still dormant but ready to roar to life, and a banged up Panthers defense is their perfect prey. Carolina made Deshaun Watson and the Browns look good last week, and allowed 59 points to the Bears in Week 1. Their defense is a serious concern, and I simply don’t trust Bryce Young to keep pace with this stacked Lions offense. Once the public realizes how injured an already struggling Panthers defense is, this line will balloon.

Pick: Detroit Lions (-3.5)

Season Record: 4-5

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Start:	September 29, 2026 @ 6:30 PM
Expert:	Scott Spreitzer
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NFL Betting Predictions: Week 4 Opening Line Report and Best Bets

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