The N.F.L.’s first international game since 2019. A rematch of last season’s A.F.C. Championship game. Bitter N.F.C. West rivals battling it out.

It will be hard to follow up the theater of last week’s Brady-Belichick chess match in New England, but with a slate of divisional matchups and up-and-coming conference opponents, the results of Week 5 could affect positioning and home-field advantages when the playoffs start in January. Every week is important, even if it isn’t hyped up with an Adele preview.

Here’s a look at N.F.L. Week 5, with all picks made against the spread.

All times Eastern

Here’s what you need to know:

• Thursday’s Matchup
• Sunday’s best games
• Sunday’s Other Games
• Monday’s Matchup
• How Betting Lines Work

Thursday’s Matchup

Los Angeles Rams at Seattle Seahawks,

Line: Rams -1 | Total: 54

The first meeting this season of two of the league’s biggest rivals will be decided by which version of the Rams’ defense shows up.

A unit that prides itself on limiting explosive plays allowed the Cardinals to amass 465 yards of total offense and score 37 points last week. Russell Wilson is just as capable of producing similar numbers if the Rams (3-1) do not correct their mistakes. Seattle (2-2), though, features a defense that ranks last in the N.F.L. in yards allowed, but played just well enough in Week 4 to beat the 49ers and rookie quarterback Trey Lance. Expect the Rams’ defensive coordinator, Raheem Morris, to shore things up after an embarrassing performance. Pick: Rams -1

Sunday’s best games

Buffalo Bills at Kansas City,

Line: Kansas City -2.5 | Total: 56.5

Patrick Mahomes vs. Josh Allen hysteria will fill the game’s broadcast, but in this rematch of last year’s A.F.C. championship, pay attention to the Bills’ defense. The unit is No. 1 in yards allowed per game (216.8), takeaways (11) and has shut out two opponents. In prime time, the Bills (3-1) can display that effectiveness, especially if they limit Kansas City receiver Tyreek Hill. The Chargers and the Ravens each limited Hill to less than 100 yards, a major factor in both of Kansas City’s losses. After losing to Kansas City (2-2) twice last season, Buffalo may now have a blueprint for securing an upset. Pick: Bills +2.5

Cleveland Browns at Los Angeles Chargers,

Line: Chargers -1.5| Total: 48.5

Expect to see a lot of Nick Chubb and Kareem Hunt in this one.

The Browns (3-1) lead the league in rushing yards per game (177) while the Chargers (3-1) allow the fourth-most rushing yards per game (139.5). Cleveland’s coupling of a strong ground attack and a defense tied for second in sacks (14) — largely thanks to the pairing of Myles Garrett and Jadeveon Clowney — may make it the most physical team in the N.F.L. Chargers quarterback Justin Herbert has shown he can keep pace with any team, but this defensive front will be a challenge, especially if the Browns’ running backs chew clock and force him into predictable passing situations. Pick: Browns +1.5.

San Francisco 49ers at Arizona Cardinals,

Line: Cardinals -5.5 | Total: 50

They planned for this.

The 49ers (2-2) drafted Trey Lance with the No. 3 overall pick this year because of Jimmy Garoppolo’s injury history. Lance may start this week against the Cardinals (4-0) though Coach Kyle Shanahan said Garoppolo (calf) and left tackle Trent Williams (shoulder) have a chance to play.

Still, San Francisco’s task in this one will be to match the extraordinary offensive output of Arizona, which leads the N.F.L. with 35 points per game and last week carved up the Rams’ defense. To keep up, Shanahan will lean on either a rookie or a less-than-100-percent Garoppolo to go throw-for-throw with the best offense in the league. With how hot Arizona is right now, that’s a risky bet. Pick: Cardinals -5.5.

Green Bay Packers at Cincinnati Bengals,

Line: Packers -3.5 | Total: 49.5

These Packers (3-1) aren’t the Jaguars, and if the Bengals (3-1) again start slow like they did last week, there won’t be another second-half comeback. Aaron Rodgers’s nonchalant attitude after Green Bay’s Week 1 blowout defeat against the Saints has yielded three straight wins since. But Cincinnati’s defense has played well in the shadow of the Joe Burrow-led offense, allowing the seventh-fewest yards (1,292) in the league. Granted, some of that total came from bolting down the Steelers’ Ben Roethlisberger and Jacksonville’s rookie quarterback, Trevor Lawrence. Doing so against a streaking Rodgers, especially if the Bengals’ attack struggles early, is a different challenge. Pick: Packers -3.5

Sunday’s Other Games

Giants at Dallas Cowboys,

Line: Cowboys -7 | Total: 52

The Cowboys (3-1) can further distance themselves from the rest of the N.F.C. East with a win over the Giants (1-3). The historically bad defense from 2020 has transformed under the first-year Dallas coordinator Dan Quinn, with its dismal passing defense saved by cornerback Trevon Diggs’s league-leading five interceptions, and the unit ranked sixth in rushing yards allowed per game (81).

Saquon Barkley, though, is the best runner the Dallas defense will have seen, and he returned to form in an overtime win against the Saints in Week 4, when he accounted for 126 all-purpose yards and two touchdowns. More impressively, the Giants won without two of their top receivers, Sterling Shephard and Darius Slayton, who are still questionable with hamstring injuries.

Three of the last five matchups between these two divisional rivals have been decided by one score. Momentum is a real thing, and even though Dallas is the better team, the Giants could make it competitive. Pick: Giants +7

Jets at Atlanta Falcons (sort of),

Line: Falcons -3.5 | Total: 44

The N.F.L. returns to London for the first time since the start of the pandemic with a matchup most Americans will sleep through or miss for a church service.

This early meeting between two 1-3 teams is more important for draft positioning than anything else. Last week, the Jets narrowly won their first game against a handicapped Titans team in overtime, fueled by the defense’s seven sacks. The unit could have another solid outing if it generates pressure on Matt Ryan and the Falcons’ pass-first attack. Zach Wilson, the Jets’ rookie quarterback, still leads the league in interceptions (8), but he took a major developmental step in last week’s win. If he continues to take care of the ball, connects on a deep throw or two, and the defense plays well again, the Jets could start a streak. Pick: Jets +3.5

Detroit Lions at Minnesota Vikings,

Line: Vikings -8 | Total: 49.5

This should be a bounce-back game for the Vikings (1-3), coming off another one-score loss to a playoff-caliber opponent. The Lions (0-4) have been competitive in each game, but have committed so many turnovers at key moments that they now seem inevitable. Kirk Cousins was battered in a loss to the Browns last week, when he was sacked twice and hit 10 times. But the Lions do not have Myles Garrett, and you can guess with confidence that Jared Goff will fumble or throw an interception giving the Vikings an extra possession. Pick: Vikings -8

Denver Broncos at Pittsburgh Steelers,

Line: Steelers -1.5 | Total: 40.5

It’s unclear whether Teddy Bridgewater will clear the concussion protocol, meaning Denver (3-1) could be forced to rely on Drew Lock’s inconsistent decision-making for this game. Lock, though, is at least able to throw the ball downfield, unlike the Steelers’ Ben Roethlisberger, whose 11 passes of over 20 yards is tied for last in the league. Until Pittsburgh (1-3) can generate a legitimate deep threat, expect defenses to keep them in check. Pick: Broncos +1.5.

Miami Dolphins at Tampa Bay Buccaneers,

Line: Bucs -10.5 | Total: 47.5

After Tom Brady’s emotional return to New England last week, the Bucs (3-1) get a more mundane visit from a Dolphins (1-3) team that produced just 203 yards of offense against the Colts. Adding to Miami’s struggles, Coach Brian Flores said Monday that receiver Will Fuller V would be unavailable Sunday after reportedly breaking his finger, and the team placed him on injured reserve.

Tampa Bay’s secondary is also contending with injuries, potentially losing cornerback Carlton Davis (leg) and safety Antoine Winfield Jr. (concussion). But the Dolphins’ pass rush isn’t strong enough to stop Brady from covering the spread. Pick: Bucs -10

New Orleans Saints at Washington Footballers,

Line: Saints -1| Total: 44.5

The Saints (2-2) blew out a Super Bowl contender. They also lost in overtime to a winless opponent.

New Orleans is perhaps the N.F.L.’ s biggest enigma, playing up or down to the competition while waiting for the return of starters like receiver Michael Thomas and defensive tackle David Onyemata. The Footballers’ (2-2) defense has also underperformed, even as Taylor Heinicke led two game-winning drives in their past three games. That’s the opposite of the defense-driven formula that carried Washington to the playoffs last season. While Washington waits for the unit to reawaken, the Saints should keep this one close and, with flipped-flopped results each week, a New Orleans win fits the pattern. Pick: Saints -1

Philadelphia Eagles at Carolina Panthers,

Line: Panthers -4 | Total: 45

Carolina Coach Matt Rhule said running back Christian McCaffrey (hamstring) will practice this week, but the Panthers (3-1) may not need to rely on him to defeat the Eagles (1-3). Defensively, they added veteran leadership through a trade with New England for cornerback Stephon Gilmore, a four-time Pro Bowl selection. Quarterback Sam Darnold leads the N.F.L. in rushing touchdowns (5) and receiver D.J. Moore is fourth in receiving yards (398). That blossoming connection could exploit an Eagles defense that allowed Kansas City receiver Tyreek Hill to score three touchdowns last week and that is tied for the sixth-most passing touchdowns allowed (9). With or without McCaffrey, the Panthers should be able to cover easily at home. Pick: Panthers -4

Tennessee Titans at Jacksonville Jaguars,

Line: Titans -4 | Total: 48.5

Urban Meyer’s embarrassing week should get worse Sunday, if the Titans (2-2) extend Jacksonville’s (0-4) losing streak. Shad Khan, the Jaguars’ owner, addressed the viral video of Meyer cavorting with a woman in an Ohio bar this week, saying the coach “must earn our trust and respect” as reports suggest Meyer has lost the locker room about a quarter of the way into his first season. With so much of the organization’s time spent on that matter, it’s reasonable to assume less energy went into repairing a defense that’s allowing 312.3 passing yards per game, the third-worst rate in the league, and that ranks last in sacks (5).

It’s still unclear whether Titans receivers Julio Jones and A.J. Brown will play on Sunday, but Ryan Tannehill still threw for 298 yards without them in an overtime loss to the Jets. Unless Jacksonville wholly revamps its defensive ineffectiveness in the span of a week filled with distractions, expect the Titans to win. Pick: Titans -4

New England Patriots at Houston Texans,

Line: Patriots -9 | Total: 39.5

Mac Jones outperformed Tom Brady and the Patriots barely lost last week. His consolation prize will be bullying the Texans (1-3), who have lost three straight games. Through four weeks, Houston receiver Brandin Cooks has amassed 369 receiving yards while none of his teammates has more than 80. That colossal imbalance makes defending Houston’s attack easy. This spread is too low. Pick: Patriots -9

Chicago Bears at Las Vegas Raiders,

Line: Raiders -5.5 | Total: 48.5

Bears running back David Montgomery, the league’s fifth-leading rusher (309 yards), is expected to miss at least four weeks after spraining an ankle. That will not help rookie Justin Fields, whom Coach Matt Nagy said will start at quarterback after last week’s win over Detroit even though the veteran Andy Dalton is now healthy. The Bears (2-2) will miss Montgomery as Fields tries to throw against a pass rush led by Maxx Crosby, who is tied for second in quarterback hits (13). The Raiders (3-1), who will be motivated after losing their undefeated record, should win. Pick: Raiders -5.5

Monday’s Matchup

Indianapolis Colts at Baltimore Ravens,

Line: Ravens -7 | Total: 46

The Ravens (3-1) have won three straight and on Monday will play in their third prime time game this season. They are looking to break the N.F.L. record for most consecutive games with 100 rushing yards.

Baltimore’s defense came up with five sacks in a victory over the Broncos last week and will look to replicate the performance against Carson Wentz, who injured both of his ankles earlier in the season. Aside from some turnovers, Lamar Jackson has played consistently, and his durability and explosiveness make him a safe bet to put away the Colts (1-3). Pick: Ravens -7

How Betting Lines Work

A quick primer for those who are not familiar with betting lines: Favorites are listed next to a negative number that represents how many points they must win by to cover the spread. Raiders -5.5, for example, means that Las Vegas must beat Chicago by at least 6 points for its backers to win their bet. Gamblers can also bet on the total score, or whether the teams’ combined score in the game is over or under a preselected number of points.