Guess what? Tom Brady heads to Foxborough, Mass., to play the Patriots this week. You probably already knew that, though.

Brady’s return to New England pits him against Coach Bill Belichick, with whom he won six Super Bowls over two decades. Brady is back in town with a freshly acquired Super Bowl ring, needing only 68 yards to break Drew Brees’s N.F.L. record for career passing yards. But there are other grudge matches around the N.F.L. in Week 4, including an N.F.C. West showdown between the unbeaten Rams and Cardinals and a scary Browns pass rush traveling to Minnesota to try to end Kirk Cousins’ interception-less streak.

Here’s a look at N.F.L. Week 4, 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

Jacksonville Jaguars at Cincinnati Bengals,

Line: Bengals -7.5 | Total: 45.5

The Jaguars’ streak of allowing an average of 302.3 passing yards per game should continue this week against the Bengals (2-1) as Joe Burrow and Ja’Marr Chase seem to have rediscovered their college chemistry in the pros.

Burrow and Chase have connected for touchdown passes in each of their three games, including two last week in the 24-10 dismantling of the Pittsburgh Steelers. Trevor Lawrence’s acclimation to the league has been rough; the rookie has thrown seven interceptions compared to only five touchdowns. Expect Burrow and the Bengals to score at will while the Jaguars (0-3) struggle to respond. Pick: Bengals -7.5

Sunday’s Best Games

Tampa Bay Buccaneers at New England Patriots,

Line: Buccaneers -6.5 | Total: 49

After the pomp and circumstance around Tom Brady’s return to Gillette Stadium as a visitor dies down, the game itself should be competitive. The Buccaneers (2-1) hope Antonio Brown can return from the reserve/Covid list, but the team will be without slot receiver Scotty Miller, who has a toe injury, and potentially pass rusher Jason Pierre-Paul, who sat out against the Los Angeles Rams with hand and shoulder injuries. Veteran free agent cornerback Richard Sherman will join the team as its secondary battles injuries, though Coach Bruce Arians said he doubted Sherman will play Sunday.

Teams have not run effectively against Tampa Bay’s front seven and have instead exploited its defensive backs. The Bucs’ secondary has allowed opponents to throw for over 300 yards twice, including in a loss to the Rams last week, when Matthew Stafford tossed for 343 yards and four touchdowns. Brady will be motivated to win, and the Bucs likely will, but the secondary’s struggles give Mac Jones and the Patriots a chance to cover the spread. Pick: Patriots +6.5

Arizona Cardinals at Los Angeles Rams,

Line: Rams -6 | Total: 54.5

Matthew Stafford’s connection with Cooper Kupp has made the receiver a fantasy-football must-have. Kupp currently leads the league in receiving yards (367), touchdown receptions (5) and is tied at first for catches (25).

Their chemistry will test the Cardinals’ defense, which has yet to face an offense as dynamic as the Rams’ (3-0). Though both teams are undefeated, the Cardinals (3-0) were saved from a loss to the Vikings in Week 2 by a shanked field goal and played down to the lowly Jaguars last week. Aaron Donald and Jalen Ramsey are unlikely to allow Kyler Murray to again put up video-game-like numbers — he’s averaging 335 yards per game — and Rams Coach Sean McVay has never lost to the Cardinals. He’ll most likely keep that streak alive. Pick: Rams -6

Cleveland Browns at Minnesota Vikings,

Line: Browns -2 | Total: 53

Kirk Cousins has yet to throw an interception so far this season, but the Browns (2-1) are the most complete defense the Vikings (1-2) will have seen.

Cousins has thrown for more than 300 yards twice, including last week while running back Dalvin Cook was out with an ankle injury. Cook’s replacement, Alexander Mattison, rushed for 112 yards in his absence. It’s still unclear whether Cook will play on Sunday, but regardless if Cook returns or Mattison starts, the Browns’ defense will be up for the challenge. The unit ranks fifth in the league against the rush (201 yards allowed) and second in sacks (14). Meanwhile, Cleveland’s offense last week welcomed back receiver Odell Beckham from his knee injury. Those factors make betting with the Vikings tough, and the spread may honestly be too low. Pick: Browns -2

Seattle Seahawks at San Francisco 49ers,

Line: San Francisco -2.5 | Total: 52

Hello, defense? Is anyone home? Pete Carroll must be asking his team that question after the Seahawks (1-2) allowed opponents to amass over 450 yards of offense in each of the last two games. No amount of Russell Wilson magic can save a game with those defensive performances.

The 49ers (2-1) will be eager to play again after narrowly losing to the Packers on a last-second field goal. But they continue to battle injuries on both sides of the ball, with important players like tight end George Kittle (calf) and Josh Norman (lungs) listed as day-to-day. If Seattle can muster some sort of respectable defensive outing for pride’s sake, then the Seahawks could manage to be competitive and cover the spread. Pick: Seattle +2.5

Baltimore Ravens at Denver Broncos,

Line: Broncos -1 | Total: 44

Their undefeated record has come against winless opponents, so the Broncos (3-0) will try to get a statement win over the Ravens (2-1), who last week struggled before closing out the Lions. Denver quarterback Teddy Bridgewater will be without receiver K.J. Hamler, the Broncos’ No. 3 receiver, who tore his left anterior cruciate ligament in another big loss to the receiving corps after Jerry Jeudy was placed on injury reserve earlier in the season.

After an overtime loss to open the season, the Ravens have closed out two thrilling victories at home and on the road. They should be able to ride that momentum to give Denver its first loss. Pick: Ravens +1

Sunday’s other games

Carolina Panthers at Dallas Cowboys,

Line: Cowboys -4 | Total: 50

Losing running back Christian McCaffrey (hamstring) and cornerback Jaycee Horn (foot) should devastate the Panthers (3-0) and their chances of remaining undefeated. With McCaffrey out for “a few weeks,” according to Coach Matt Rhule, receiver D.J. Moore is the Panthers’ best offensive weapon. He’ll likely be shadowed by the Cowboys’ top cornerback, Trevon Diggs, who has had an interception in every game this season.

The Cowboys will keep up an aggressive offensive attack as offensive coordinator Kellen Moore tries to exploit a secondary that hastily added C.J. Henderson via trade this week. Until proven otherwise, expect the Panthers’ offense to backslide and struggle without McCaffrey as its workhorse. Pick: Cowboys -4

Washington Footballers at Atlanta Falcons,

Line: Footballers -1.5 | Total: 48

Oddsmakers are essentially predicting a tossup between these two teams, largely because Washington has not played to its potential. The Footballers’ defense, in theory, should overpower the Falcons (1-2), as Atlanta has rushed for 100 yards only once and is still heavily relying on Matt Ryan’s arm at the ripe age of 36. But the Footballers (1-2) failed to sack Bills quarterback Josh Allen last week, and he dissected them for four touchdowns. Against a weaker offensive line, Washington should find more success. Pick: Footballers -1.5.

Houston Texans at Buffalo Bills,

Line: Bills -17 | Total: 48

The line on this game is absurdly lopsided and rightfully so. The Bills’ defense generated three turnovers in each of the last two games. They likely will feast on rookie Texans (1-2) quarterback Davis Mills, who threw for only 168 yards and was sacked four times in his first N.F.L. start last week against Carolina. Mills will likely do more to limit the production of Texans receiver Brandin Cooks than the Bills (2-1) will. Expect the score to get ugly quick. Pick: Bills -17

Detroit Lions at Chicago Bears,

Line: Bears -3 | Total: 42.5

This could finally be the one.

The Lions (0-3) have played competitively in first halves against playoff-caliber teams, and Ravens kicker Justin Tucker had to convert a record-breaking 66-yard field goal attempt to rob Detroit of a win last week. That evasive W may come against the Bears (1-2), who posted 1 net passing yard (yes, you read that correctly) and allowed the rookie Justin Fields to take nine sacks against the Browns. Coach Matt Nagy said Fields, Andy Dalton and Nick Foles are all under consideration to start. The Lions could capitalize on that dysfunction. Pick: Lions +3

Indianapolis Colts at Miami Dolphins,

Line: Dolphins -1.5 | Total: 43.5

Injuries continue to plague the Colts (0-3), most recently with All-Pro offensive guard Quenton Nelson spraining his ankle and needing to be carted off the field last week. Coach Frank Reich did not rule Nelson out, but said his chances of playing are “not looking good.” Nelson’s availability would help against the Dolphins (1-2), who feature an aggressive and opportunistic defense. Miami backup quarterback Jacoby Brissett completed over 65 percent of his passes in an overtime loss to the Raiders in Week 3, showing he can manage the offense efficiently while Tua Tagovailoa’s ribs heal. If that responsible play continues and the defense generates pressure and turnovers, the Carson Wentz experiment in Indianapolis could remain winless. Pick: Dolphins -1.5

Giants at New Orleans Saints,

Line: Saints -7.5 | Total: 43.5

Giants receivers Sterling Shepard and Darius Slayton both injured their hamstrings in Week 3, potentially removing two of Daniel Jones’s favorite targets. He’ll need every asset the Giants (0-3) can give offer to combat the inevitable deafening noise in the Superdome for the Saints’ first true home game of the season. The Saints (2-1), whose defense collected three interceptions last week against the Patriots, could produce a similar outing as Jones throws to pass catchers on the bottom of the depth chart. Pick: Saints -7.5

Tennessee Titans at Jets,

Line: Titans -7.5 | Total: 46

Receiver A.J. Brown’s hamstring injury should not stop the Titans (2-1) from winning this game easily, given the team’s other formidable stars, running back Derrick Henry and receiver Julio Jones. The Jets, however, lack such options. Rookie quarterback Zach Wilson has thrown seven interceptions to two touchdowns and the Jets (0-3) have rushed for more than 100 yards only once. Even a developing defense like Tennessee’s should be able to contain the Jets’ attack. Pick: Titans -7.5

Kansas City at Philadelphia Eagles,

Line: Kansas City -6 | Total: 54.5

Kansas City (1-2) has suffered back-to-back losses only three times since 2018, making this uncommon territory for a perennial Super Bowl contender. They most likely will bounce back this week against the Eagles (1-2), who took a thorough beating from Dallas on Monday and face a short week to prepare.

Kansas City Coach Andy Reid reportedly returned to work Tuesday after being treated for dehydration after Sunday’s game. He most likely will preach ball security to his team, which committed six total turnovers in losses to the Ravens and the Chargers. If the Chiefs can fix those issues, their firepower should be too much for the Eagles’ young offense to respond. Pick: Kansas City -6

Pittsburgh Steelers at Green Bay Packers,

Line: Steelers -6.5 | Total: 45.5

The Steelers’ pedestrian offense has been a problem and now faces a Packers (2-1) team that is beginning to click. Pittsburgh’s quarterback weakness has been well documented, but Ben Roethlisberger ranks third in the N.F.L. in passing attempts in large part because the team has yet to rush for more than 75 yards in a game this season and its defense has given up first-quarter leads.

The Steelers (1-2) are hopeful outside linebacker T.J. Watt (groin) will be available after missing last week’s loss to the Bengals, but Aaron Rodgers’s output should still far exceed that of the Steelers’ offense. Pick: Packers -6.5

Monday’s Matchup

Las Vegas Raiders at Los Angeles Chargers,

Line: Chargers -3.5 | Total: 52.5

With Kansas City figuring out how to end their rut and the Broncos facing their first winning opponent, the Chargers or Raiders will gain valuable ground in the A.F.C. West. The outcome will come down to whether the Chargers’ new-look offensive line can hold its own against the Raiders’ improved pass rush. The Chargers (2-1) have allowed only five sacks, but Los Angeles’s offense leads the league in penalty yards (243), including notable flags for illegal shifts in a loss to the Cowboys and a narrow win over the Chiefs.

This one will have exceptional player matchups to watch — between Chargers rookie tackle Rashawn Slater and Raiders defensive end Maxx Crosby, and Chargers safety Derwin James against Raiders tight end Darren Waller — but the Raiders (3-0) may have the edge if running back Josh Jacobs returns after missing two games with an ankle injury. Pick: Raiders +3.5

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. Steelers -4.5, for example, means that Pittsburgh must beat Cincinnati by at least 5 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.