The last week of the preseason is here and before you know it we'll be off to the races with the start of the 2021 regular season. While we're still a few weeks away from the Sept. 9 opener between the Cowboys and Bucs, it's never too early to take a look at the Week 1 slate and begin formulating our picks. Here, I'll comb through a handful of games that especially catch my eye and also give my early leans for the entire opening weekend in the NFL. 

Of course, these picks are subject to change as we get closer to Week 1 and are merely where I'm leaning at the moment prior to the exhibition season coming to a close. Nevertheless, there's some pretty solid value on the board right now, which we'll cover. 

All NFL odds via Caesars Sportsbook. 

49ers at Lions

I do think we forget about the San Francisco 49ers a little bit when talking about the powerhouses in the NFC. That could be thanks to a looming quarterback change from Jimmy Garoppolo to rookie Trey Lance, but that shouldn't overshadow how solid of a team this is from top to bottom. More importantly, the Niners are healthy, which is something that you couldn't say for the bulk of last year. 

That defense -- led by Nick Bosa and Fred Warner -- should have no problem going on the road and handling a Lions team that is not only entering 2021 with a new head coach in Dan Campbell and a new quarterback in Jared Goff, but they're also a little dinged up. Both running back D'Andre Swift and tight end T.J. Hockenson have been dealing with injuries this summer. Even if they are ready for the opener, it doesn't look like they'll be 100%. Those two are expected to be key cogs in Detroit's offense this season, so with them limited in Week 1, it's shaping up to be a long day for the Lions. 

No ad available

San Francisco also has played well historically to begin the year. The team is 7-3 ATS in their last 10 games in Week 1 and is 5-2 ATS in their last seven games in September. 

Projected score: 49ers 28, Lions 17
The pick
: 49ers -7.5 

Broncos at Giants

It'll be Teddy Bridgewater under center for the Broncos in the opener after the team recently named him the starting quarterback for Week 1 after beating out Drew Lock this summer. Denver has a ton of weapons offensively that Bridgewater can lean on and should prove to be a unit that's tough to contain, especially if the veteran quarterback is as efficient as he was during the preseason. Through two contests, Bridgewater completed 16 of his 19 passes for 179 yards two touchdowns. 

Not only does Bridgewater's ascension to QB1 bring promise to the Broncos, but it's also an encouraging sign for bettors. For his career, Bridgewater has been otherworldy to those who lean on him, owning a 35-14 ATS record in his starts. To look at it even deeper and link it to the opener at MetLife Stadium, Bridgewater is 21-3 ATS when he plays on the road. That's enough to have anyone blindly throw a few shekels on Denver here. It also doesn't hurt that New York is 0-4 ATS in their last four games in Week 1 and likely won't have a few key pieces to its offense (Saquon Barkley, Kadarius Toney, and Kenny Golladay) 100% healthy for this matchup. 

No ad available

Projected score: Broncos 24, Giants 17
The pick: Broncos -1.5

Bears at Rams

Bears head coach Matt Nagy is insistent that Andy Dalton will get the start in the opener against Los Angeles, despite the promise that first-round rookie Justin Fields has shown over the summer. That could, in part, be due to Chicago not wanting to expose its young quarterback to the lethal Rams defense right out of the gate, simply feeding Dalton to the wolves. L.A. continued to be one of the league's better defenses last year, ranking fourth in DVOA, and should once again be a unit that has the ability to completely wreck a game. The Bears offensive line also has looked a bit suspect throughout periods of the preseason, which only adds more confidence towards Aaron Donald's club. Meanwhile, the Rams are about to unwrap their new high-powered offense led by quarterback Matthew Stafford, who the team acquired this offseason. Given the Bears' limited ceiling offensively under Dalton and against this L.A. defense, Chicago could be left in the dust pretty quickly in this one. 

Of course, there's also a Sean McVay factor here as well as he routinely has his teams well-prepared on a weekly basis, but especially when he has more time to prepare. Throughout his previous four years as the Rams head coach, McVay is 4-0 ATS in Week 1. 

Projected score: Rams 30, Bears 20
The pick: Rams -7.5

Browns at Chiefs 

The Cleveland Browns are a team that could very well take a leap in 2021. After making the playoffs last season and advancing to the Divisional Round, the team went out this offseason and added a number of players that should only improve the club as a whole. Also, Year 2 under head coach Kevin Stefanski should bring even more stability to the organization. That said, it's tough to look away from the Chiefs here. They are looking to rebound from a loss in Super Bowl LV and will do so with an entirely revamped offensive line. If that new collection of linemen -- headlined by guard Joe Thuney and tackle Orlando Brown -- can keep Patrick Mahomes upright, they should be able to keep a touchdown distance over the Browns. 

No ad available

K.C. is another club that routinely begins the year off strong. Not only are they 4-0 ATS in their last four Week 1 contests, but they are 12-2 ATS in their last 14 games in September. 

Projected score: Chiefs 28, Browns 21
The pick: Chiefs -6

Cardinals at Titans

The Cardinals are my upset pick on the Week 1 slate. The Titans are poised to be players in the AFC playoff race again this season, but I'm not so sure what they'll look like out of the gate. Both receivers A.J. Brown and Julio Jones have been missing time in practice due to injury, which means they may not be a full-go in the opener. If that's the case, Ryan Tannehill's weapons in the passing game become extremely limited and will likely need Derrick Henry to have a monster outing to help bail them out. While Tennessee did add the likes of Bud Dupree to help its defense, it remains to be seen how much the pass rusher -- who tore his ACL in Week 12 last season -- will be able to truly impact the unit from the jump. In 2020, the Titans ranked as the fourth-worst defense in the NFL in DVOA. Even if they marginally improve, they'd still be in the bottom half of the league. The Titans also don't have the best track record to begin the year, owning a 1-4 ATS mark in their past five Week 1 contests. In their last six games in September, they are 1-5 ATS. 

Given all those factors, it's easy for me to fade Tennessee at the moment. As long as the Cardinals -- who are 4-0 ATS against the Titans in their last four meetings -- don't choke it away, they have the talent on both sides of the ball to not only cover but possibly win outright. 

No ad available

Projected score: Cardinals 27, Titans 24
The pick: Cardinals +3

Rest of the bunch

Cowboys at Buccaneers
Projected score: Buccaneers 30, Cowboys 20
My pick: Buccaneers -7.5

Eagles at Falcons
Projected score: Falcons 24, Eagles 20
My pick: Falcons -3.5

Steelers at Bills
Projected score: Bills 27, Steelers 21
My pick: Steelers +7

Vikings at Bengals 
Projected score: Vikings 30, Bengals 27
My pick: Bengals +3.5

Seahawks at Colts
Projected score: Seahawks 27, Colts 17
My pick: Seahawks -1

Chargers at Washington
Projected score: Chargers 24, Washington 21
My pick: Chargers -1.5

No ad available

Jets at Panthers
Projected score: Panthers 27, Jets 17
My pick: Panthers -4.5

Jaguars at Texans 
Projected score: Jaguars 24, Texans 20
My pick: Jaguars -3

Dolphins at Patriots
Projected score: Patriots 23, Dolphins 20
My pick: Patriots -2.5

Packers at Saints
Projected score: Packers 33, Saints 24
My pick: Packers -3

Ravens at Raiders
Projected score: Ravens 28, Raiders 21
My pick: Ravens -4