Underdogs played a huge role in Week 1, going 12-4 against the spread with nine wins outright. The Pittsburgh Steelers, 6½-point underdogs, beat the Buffalo Bills, 23-16. The Philadelphia Eagles were 3½-point underdogs on the road against the Atlanta Falcons and won, 32-6. The New Orleans Saints, also 3½-point underdogs, enjoyed a 38-3 blowout against Aaron Rodgers and the Green Bay Packers. The Arizona Cardinals and Houston Texans also joined in on the fun.

The first week of the season often isn’t kind to NFL favorites. Since 2002, when the league expanded to 32 teams, favorites have a 146-160-12 record against the spread on opening weekends for a .477 winning percentage. Week 2 is even worse, with favorites covering just 45 percent of the time. However, there is at least one favorite this week that’s worth backing to buck the trend.

To determine the value of a spread wager, we use the preseason point spreads released by various oddsmakers to set a preliminary power ranking for each team, which is then compared to its opponent and adjusted for location. The result is a projected margin of victory, which is compared to the actual point spread for the week. The preliminary power rankings are phased out as the season progresses, making sure each team’s strength is a full reflection of its overall performance.

Picks are against the consensus point spreads as of Wednesday afternoon.

Buffalo Bills (-3½) at Miami Dolphins

Pick: Bills -3½

The Steelers dealt the Bills an ugly loss at home, but it’s fair to expect last year’s AFC finalists to rebound this week. Buffalo gave up a touchdown on a blocked punt last week and also had an interception and two turnovers on downs. However, this is still the fourth-most-talented team of 2021, per Pro Football Focus, and quarterback Josh Allen could take advantage of Miami’s third-down defense much like New England did in Week 1.

The Patriots converted 11 of 16 third-down opportunities against the Dolphins on Sunday, while Allen finished with the second-highest third-down completion rate (67 percent) of 35 qualified passers last season.

It’s worth shopping around to see if you can get the Bills favored by three points, as three is a key number, with 15 percent of regular season games since 2015 ending with a scoring margin of exactly three points. Still, it wouldn’t be surprising if Buffalo won by a touchdown or two.

Los Angeles Rams (-4) at Indianapolis Colts

Pick: Colts +4

This should be an epic battle in the trenches. Rams defensive lineman Aaron Donald, a four-time Pro Football Focus defensive player of the year, will have to deal with the Colts’ Quenton Nelson, the fourth-highest-rated guard of 2020 per PFF. Nelson also anchors PFF’s projected second-best offensive line of 2021, and that was without taking into account left tackle Eric Fisher, who missed Week 1 with an Achilles’ injury. Colts Coach Frank Reich hasn’t ruled out Fisher, a two-time Pro Bowl pick and a Super Bowl winner with the Kansas City Chiefs, for Week 2.

If Indianapolis can improve its pass protection for Carson Wentz a little bit — he was sacked three times and under pressure on 20 of his 44 drop-backs in the opening loss to Seattle — the Colts could keep it close.

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The plays above represent our best bets of the week because our analysis shows their value is the most lucrative compared to what we expect to happen once the teams take the field. Below, you will find against-the-spread picks for all of the games on this week’s schedule. However, trying to pick every single game is something of a fool’s errand. The house wins so often partly because bettors try to make too many plays when the odds aren’t in their favor. Keep that in mind when evaluating the remaining games from the Week 2 slate.

New York Giants at Washington Football Team (-3)

Pick: Washington -3

Cincinnati Bengals at Chicago Bears (-2½)

Pick: Bengals +2½

Denver Broncos (-6) at Jacksonville Jaguars

Pick: Broncos -6

Houston Texans at Cleveland Browns (-12½)

Pick: Texans +12½

Las Vegas Raiders at Pittsburgh Steelers (-5½)

Pick: Raiders +5½

New England Patriots (-5½) at New York Jets

Pick: Patriots -5½

New Orleans Saints (-3½) at Carolina Panthers

Pick: Saints -3½

San Francisco 49ers (-3½) at Philadelphia Eagles

Pick: Eagles +3½

Atlanta Falcons at Tampa Bay Buccaneers (-13)

Pick: Falcons +13

Minnesota Vikings at Arizona Cardinals (-4)

Pick: Cardinals -4

Dallas Cowboys at Los Angeles Chargers (-3)

Pick: Chargers -3

Tennessee Titans at Seattle Seahawks (-5½)

Pick: Titans +5½

Kansas City Chiefs (-3½) at Baltimore Ravens

Pick: Ravens +3½

Detroit Lions at Green Bay Packers (-11)

Pick: Packers -11