The NFL appears to be back-loading its schedule with divisional games as, for the second week in a row, there are just two divisional matchups you can target in NFL betting and Week 6 NFL picks. Only one is on Sunday, with the Steelers vs. Browns (+5.5), and both teams played the Vikings in Europe in their last games, though in different weeks. Other Week 6 NFL spreads of at least 5 points include Rams vs. Ravens (+7.5), with Lamar Jackson’s availability in doubt, Jets vs. Broncos (-7.5) in London, Colts vs. Cardinals (+6.5) and Packers vs. Bengals (+14), in which Joe Flacco will make his Cincy debut under center.

The last of those matchups is the seventh game this year with an NFL line of more than 9 points, and heavy favorites are 3-3 ATS in those matchups. Thus, that NFL betting trend won’t help much with your Week 6 NFL predictions, but there are others that could certainly assist with football bets. All of the updated Week 6 NFL lines are listed below, and SportsLine’s advanced computer model has all the NFL betting advice and NFL predictions you need to make the best Week 6 NFL picks now. 

New users can also target the DraftKings promo code, which offers $200 in bonus bets instantly if your bet wins:

The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on top-rated NFL picks since its inception. The model is on a sizzling 41-21 run on top-rated picks dating back to 2024. Anybody following its NFL betting picks at sportsbooks and on betting sites could have seen strong returns.

Now, it has turned its attention to the latest Week 6 NFL odds and NFL betting lines and locked in betting picks for every NFL matchup. Head here to see every pick. 

New users can also check out the latest FanDuel promo code and get $300 in bonus bets instantly at FanDuel if your $5 bet wins:

Top Week 6 NFL predictions

We can tell you one of the model’s strongest Week 6 NFL picks is that the Cowboys (-3, 49.5) cover the spread versus the Panthers in a Sunday 1 p.m. ET kickoff. Dallas has overcome CeeDee Lamb’s absence with 77 points over its last two games, both of which it covered. Dak Prescott has eight total touchdowns, versus zero turnovers, over this span and his completion percentage over 2025 is the highest of his career. He’s being assisted by a dominant run game that ranks in the top 10 in both yards per game and yards per carry after ranking 27th or worse in both in 2024.

Dallas should feast off a Carolina defense which has the fewest sacks (five) in the NFL and the lowest pressure rate. Carolina isn’t much better on offense, ranking 24th in scoring and 26th in passing yards. The Panthers did win last week, but Bryce Young has followed up each of his last four victories with straight-up defeats. The model has Dallas prevailing versus the spread almost 60% of the time in an A-rated pick. See which other teams to pick here.

Another one of its Week 6 NFL predictions: the Buccaneers (-3, 47.5) cover versus San Francisco in over 50% of simulations. Between their juggling of quarterbacks, just six teams have a worse turnover differential than the 49ers, who are also getting next to nothing in their run game. The team is dead last in yards per carry, and a one-dimensional offense may struggle to keep up with the Bucs. Baker Mayfield owns a 10:1 TD:INT, and Tampa ranks in the top 10 in both scoring offense and total offense.

San Fran does have a few extra days of rest after playing last Thursday, but that hasn’t necessarily been an omen to spread success. The team is just 2-4 ATS with a rest advantage over its last six games, and one can’t ignore the cross-country flight that the Niners will have to make. San Francisco played three games on the East Coast last season and failed to cover in all three. The model also says the Over hits well over 50% of the time. See which other teams to pick here.

How to make Week 6 NFL picks

The model has also made the call on who wins and covers in every other game on the Week 6 NFL schedule and just revealed five teams that win by double-digits, potentially giving you a huge payday. You can only get every pick for every game at SportsLine.

So what Week 6 NFL picks can you make with confidence, and which five teams should you lock in now? Check out the latest NFL odds below, then visit SportsLine to see which teams win and cover the spread, all from a proven computer model that has returned well over $7,000, and find out.

Week 6 NFL betting odds, lines, live spreads, scores

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