Week 5 was a fruitful week for Sporting News’ picks and predictions against the spread. With one month and four games of data on every team, it was a little easier to figure out a few things. 

Even so, there were dramatic, one-possession endings for the Jets-Vikings, 49ers-Cardinals, Bengals-Ravens, and Cowboys-Steelers that didn’t go in our favored team’s favor. Anomalous results will happen because of defensive takeaways and unforeseen offensive and special teams miscues.

That’s built into every slate of games, every week. You will win some, you will lose some — the goal is just to win more than you lose. Sounds simple, right, but it’s a lot tougher than that. Here’s fearlessly diving into the Week 6 forecast of professional pigskin prognostications:

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(Odds courtesy of Caesars Sportsbook)

MORE: Week 6 NFL Power Rankings | Week 6 NFL picks

NFL picks against the spread for Week 6

• Game of Midweek: 49ers (-3, 47.5 o/u) at Seahawks

Thursday 8:15 p.m. ET, Amazon Prime Video

The Seahawks started 3-0 and have cooled off to 3-2. The 49ers started hot vs. the Jets but have fallen to 2-3. Someone will gain the early edge in an NFC West race that seems weaker than expected with the Rams struggling and the Cardinals limited. The key for both Geno Smith and Brock Purdy is avoiding backbreaking turnovers, as both defenses have proved to be vulnerable in key spots. The 49ers will have more rushing success with Jordan Mason to support their QB, making the difference in a hostile road environment on a short week.

Pick: 49ers win 24-20 and cover the spread.

MORE: Brock Purdy struggled when 49ers needed him most | Injuries killing 49ers ahead of daunting schedule

• Game of the Week: Commanders at Ravens (-6.5, 52.5 o/u)

Sunday 1 p.m. ET, CBS

This is the best Battle of the Beltway ever with Heisman-winning, dual-threat MVP candidate Jayden Daniels facing off with Heisman-winning dual-threat two-time MVP Lamar Jackson. The defenses have started to show plenty of holes, meaning the offensive fireworks of chunk runs and big pass plays will not disappoint. Jackson’s experience and help from Derrick Henry give him a slight edge over Daniels, who is still on the road despite a short local trip.

Pick: Ravens win 31-27 but fail to cover the spread.

MORE: Jayden Daniels for OROY? Try NFL MVP

• Lock of the Week: Steelers (-3, 36.5 o/u) over Raiders

Sunday 4:05 p.m. ET, CBS

The Steelers had it rough on the road against the Colts and at home vs. the Cowboys, as their run-heavy formula fueled by Justin Fields failed with the defense getting worn down late. Here, they don’t need to worry about a real run defense or a real passing game, as the Black and Gold dominate the Silver and Black in the crowd for what will feel like a Vegas road trip. Fields will show up his former offensive coordinator, Luke Getsy, working for the other side with a 100-yard rushing game while T.J. Watt wreaks havoc on whoever starts at QB for the Raiders.

Pick: Steelers win 27-10 and cover the spread.

MORE: Raiders QB depth chart

• Upset of the Week: Buccaneers (+2, 45.5 o/u) over Saints

Sunday 1 p.m. ET, Fox

The Saints will be coming off a short week, and the Buccaneers will be coming off a mini-bye, feeling well-rested after playing overtime last Thursday night. Baker Mayfield will keep playing well in another away dome in the division, this time with better results. The defense digs deeper to slow down Alvin Kamara, then makes a game-sealing play vs. Derek Carr.

Pick: Buccaneers win 27-24.

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Matt Marton

• Jaguars at Bears (-2, 44.5 o/u)

Sunday 9:30 p.m. ET, NFL Network (in London)

It took 2021 No. 1 overall pick Trevor Lawrence celebrating his 25th birthday last Sunday to put up a needed big game to lift Jacksonville to its first victory of the season. But there’s no winning streak in Jacksonville’s home away from home in London. The Bears have gotten hot with 2024 No. 1 overall pick Caleb Williams, who will take advantage of another weak pass defense with his streamlined weapons, DJ Moore, D’Andre Swift, and Cole Kmet. Even more good rushing success from the Jaguars won’t be enough across the pond.

Pick: Bears win 24-20 and cover the spread.

MORE: DJ Moore, Caleb Williams remind Panthers of Bryce Young trade | Trevor Lawrence-Gabe Davis sideline spat 

• Cardinals at Packers (-5, 49.5 o/u)

Sunday 1 p.m. ET, Fox

The Packers’ defense is making huge plays and forcing takeaways under new ace defensive coordinator Jeff Hafley, led by star free-agent addition Xavier McKinney. McKinney will be looking to capitalize on Kyler Murray’s mistakes after Green Bay’s front contains him as a runner. Jordan Love breaks out of a turnover slump big time by going back to basics and playing off the run well with more efficient downfield passing at home.

Pick: Packers win 27-20 and cover the spread.

MORE: Xavier McKinney nears NFL-record INT streak

• Texans (-7, 37.5 o/u) at Patriots

Sunday 1 p.m. ET, CBS

The Texans will come in still battling some key injuries around C.J. Stroud, but they should be leaning plenty on the running game and defense in a positive game script. Stroud will face a few tough elements from Jerod Mayo’s defense, but Houston’s run blocking will compensate well with whoever’s in the backfield. With the Patriots considering starting Drake May at QB, they can get a little spark to make it closer than the score indicates in garbage time.

Pick: Texans win 23-20 but fail to cover the spread.

MORE: Nico Collins injury update

Photo by Chris Graythen/Getty Images

• Browns at Eagles (-8.5, 43 o/u)

Sunday 1 p.m. ET, Fox

The Eagles will come out of the bye with better passing-game health and a pressure defense that will come together better for DC Vic Fangio. Nick Sirianni can cool off his hot seat while making things even warmer for Kevin Stefanski. Look for Jalen Hurts to have a big all-around game as Cleveland’s front also gets pushed around up front for a rested Saquon Barkley and the running game. Deshaun Watson may finally prompt a change with a little more poor play on the road in the NFC East again.

Pick: Eagles win 27-17 and cover the spread.

MORE: Will Deshaun Watson be benched? | Will Browns fire Kevin Stefanski?

• Colts (-1, 42.5 o/u) at Titans

Sunday 1 p.m. ET, CBS

Will Anthony Richardson (oblique) and Jonathan Taylor (ankle) return at the same for the Colts after missing one game? Joe Flacco was an OK pass-happy fill-in, so that makes Taylor a little more important after not being able to close well in Jacksonville. The Titans will have a few more offensive answers under Brian Callahan by continuing to lean more on running backs Tony Pollard and Tyjae Spears, but either Will Levis or Mason Rudolph will make one too many mistakes in relation to Flacco or Richardson.

Pick: Colts win 20-17 and cover the spread.

MORE: Joe Flacco earns ‘Jamar Flaccson’ nickname after 21-yard scramble

• Chargers (-3, 35.5 o/u) at Broncos

Sunday 4:05 p.m. ET, CBS

There’s one simple key to beating Denver: Running the ball and doing it some more. The Broncos’ defense has been making plays vs. the pass, but teams are trying to throw too much on a fraudulent 3-2 team that gives up a league-high 5.0 yards per carry.  Jim Harbaugh and Greg Roman will relentlessly run with a rested JK Dobbins and Gus Edwards off a bye, and Jessie Minter will have had time to cook up some confusion for Bo Nix.

Pick: Chargers win 23-10 and cover the spread.

MORE: Bo Nix, Sean Payton have animated sideline argument

• Falcons (-6, 47.5 o/u) at Panthers

Sunday 4:25 p.m. ET, Fox

The Falcons have their passing game in full gear and will rip this secondary to shreds over the short, intermediate, and deep areas with Kirk Cousins now locked into all three key receivers (Drake London, Darnell Mooney, Kyle Pitts). But this is a game for Atlanta to flex more as needed in the running game with Bijan Robinson to help protect its defense. The Panthers show more fight at home with Andy Dalton, but there’s no way they stay competitive once the game script goes negative early.

Pick: Falcons win 30-17 and cover the spread.

WEEK 6 FANTASY FOOTBALL RANKINGS
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• Lions (-3.5, 52.5 o/u) at Cowboys

Sunday 4:25 p.m. ET, Fox

The Lions will find a way to run all over Dallas with Jahmyr Gibbs and David Montgomery, but they will have limited downfield passing success with Jared Goff, which will lead to some turnovers that keep Dak Prescott and Dallas in the game. The Cowboys’ pass-happy attack will push it to the limit with Prescott picking apart plenty in Detroit’s defense, but Gibbs and Montgomery combine to close it out well in the fourth quarter.

Pick: Lions win 27-24 but fail to cover the spread.

MORE: CeeDee Lamb lets Dak Prescott hear it after ugly INT

Jeffrey Becker-USA TODAY Sports

• Bengals (-3.5, 48.5 o/u) at Giants

Sunday 8:20 p.m. ET, NBC

The Bengals’ offense needs to score plenty and pass plenty with Joe Burrow, Ja’Marr Chase, and Tee Higgins because the defense has fallen apart vs. the run and pass. The Giants’ offense has gotten hot with Daniel Jones responding well to Brian Daboll’s play-calling when not facing a tough defensive matchup. Look for Jones to keep it up, especially if Malik Nabers returns to show he can be as good of a rookie LSU receiver as Chase was. The Giants run well with whoever to stay in the game, but Burrow delivers a game-winning drive to try to save the Bengals season (again).

Pick: Bengals win 30-27 but fail to cover the spread.

MORE: Wan’Dale Robinson has IG Live video interrupted by coach Brian Daboll

• Bills (-2.5, 41.5 o/u) at Jets

Monday 8:15 p.m. ET, ESPN

The Jets need this kind of get-well home offensive matchup against a bad running back defense. The Bills are giving up 4.6 yards per carry as part of allowing 144 rushing yards per game. They also allow a league-worst 62.5 receiving yards per game to the position. That should get Breece Hall and Braelon Allen back on track to ease the pressure on Aaron Rodgers. The Jets fire first in this tough battle for first place in what’s looking like a lesser-than-expected AFC East.

Pick: Jets win 23-20.

MORE: Will Jets fire Robert Saleh? | Aaron Rodgers injury update | Sean McDermott on Bills’ costly clock management

Stats of the Week

• Week 5 record straight up: 10-5
• Week 5 record against the spread: 10-5
• Season-to-date straight up: 49-30
• Season-to-date against the spread: 37-27