The NFL has already seen 26 underdogs win outright through the first four weeks of the 2022 season, and going against the favorites has been a profitable NFL betting strategy whether you're playing the spread or the money line. Buffalo is the largest favorite on the board according to the latest Week 5 NFL odds from Caesars Sportsbook, spotting the Steelers 14 points at home. In their last seven games as double-digit favorites, Buffalo is 5-1-1 against the spread, so betting Kenny Pickett and the Steelers could be one of the riskier NFL picks and NFL bets.

The latest Week 5 NFL spreads list the Buccaneers (-10) as the only other double-digit favorite as they take on the Falcons with first place in the NFC South on the line. All of the Week 5 NFL lines are listed below, and SportsLine's advanced computer model has all the NFL betting advice and predictions you need to make the best Week 5 NFL picks now.

The model, which simulates every NFL game 10,000 times, is up almost $7,000 for $100 players on top-rated NFL picks since its inception. The model enters Week 5 of the 2022 NFL season on an incredible 140-105 run on top-rated NFL picks that dates back to the 2017 season.

The model also ranked in the top 10 on NFLPickWatch four of the past six years on straight-up NFL picks and beat more than 94% of CBS Sports Football Pick'em players four times during that span. Anyone who has followed it is way up.

Now, it has turned its attention to the latest Week 5 NFL odds and locked in picks for every NFL matchup. Head here to see every pick.

Top Week 5 NFL predictions

One of the model's strongest Week 5 NFL picks is that the Titans (-2.5) cover against the Commanders in almost 60% of simulations. Washington opened the season with a 28-22 victory over the Jacksonville Jaguars, but the Commanders have lost their last three games. Quarterback Carson Wentz has struggled after throwing seven touchdowns in his first two games. In fact, Wentz has thrown for fewer than 215 yards in his last two outings. In Sunday's loss against the Cowboys, Wentz finished with 170 passing yards, one touchdown and two interceptions.

The Titans, meanwhile, enter Sunday's matchup with confidence after winning back-to-back games. In addition, the road team is 6-0 against the spread in the last six meetings between these two franchises. The Commanders are also just 8-16 in their last 24 games at FedEx Field. That's one of the main reasons why SportsLine's model projects the Titans will cover the spread nearly 60% of the time. See which other teams to pick here.

Another one of its Week 5 NFL predictions: The Jaguars (-7) cover at home in a divisional matchup against the Texans. Jacksonville is off to a surprising 2-2 start in Doug Pederson's first season at the helm of the franchise, but the Jaguars' plus-38 scoring differential is actually third-best in the NFL.

Meanwhile, Lovie Smith's Texans are the only winless team and enter Sunday ranked 27th in total offense and 29th in total defense. Houston has been outgained in every game it's played, including the season-opening tie against Indianapolis in which it was outgained by a staggering 218 yards and blew a 17-point second-half lead.

Trevor Lawrence, James Robinson and Christian Kirk give the Jaguars a quality offensive trio that the Texans could struggle to contain. The model is predicting that Jacksonville outgains Houston by over 100 yards to help the Jaguars cover the spread in well over 50 percent of simulations. See which other teams to pick here.

How to make Week 5 NFL picks 

The model has also made the call on who wins and covers in every other game on the Week 5 NFL schedule, and it also says an underdog delivers a huge upset. You can only get every pick for every game at SportsLine.

So what NFL picks can you make with confidence? And which underdog delivers a huge upset? 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 almost $7,000 since its inception, and find out.

Week 5 NFL odds, lines, spreads

Get full NFL picks at SportsLine

Sunday, Oct. 9

Giants at Packers (-8, 41)

Featured Game | Green Bay Packers vs. New York Giants

Steelers at Bills (-14, 46.5)

Featured Game | Buffalo Bills vs. Pittsburgh Steelers

Chargers at Browns (+2.5, 47.5)

Featured Game | Cleveland Browns vs. Los Angeles Chargers

Texans at Jaguars (-7, 43.5)

Featured Game | Jacksonville Jaguars vs. Houston Texans

Bears at Vikings (-7, 44)

Featured Game | Minnesota Vikings vs. Chicago Bears

Lions at Patriots (-3, 45.5)

Featured Game | New England Patriots vs. Detroit Lions

Seahawks at Saints (-5.5, 46)

Featured Game | New Orleans Saints vs. Seattle Seahawks

Dolphins at Jets (+3.5, 46)

Featured Game | New York Jets vs. Miami Dolphins

Falcons at Buccaneers (-9, 48)

Featured Game | Tampa Bay Buccaneers vs. Atlanta Falcons

Titans at Commanders (+2.5, 42.5)

Featured Game | Washington Commanders vs. Tennessee Titans

49ers at Panthers (+6.5, 39)

Featured Game | Carolina Panthers vs. San Francisco 49ers

Eagles at Cardinals (+5, 49)

Featured Game | Arizona Cardinals vs. Philadelphia Eagles

Cowboys at Rams (-5.5, 42.5)

Featured Game | Los Angeles Rams vs. Dallas Cowboys

Bengals at Ravens (-3, 48.5)

Featured Game | Baltimore Ravens vs. Cincinnati Bengals

Monday, Oct. 10

Raiders at Chiefs (-7, 51)

Featured Game | Kansas City Chiefs vs. Las Vegas Raiders