College Football Week 1 Saturday parlay picks & predictions: Three-team parlay at mega (+774) odds: Louisville cruises past Syracuse

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Caleb Wilfinger


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Deputy Editor for Pickswise with years of experience handicapping and giving out winning picks. Lover of all US sports and Southampton FC. For Caleb Wilfinger media enquiries, please email
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After a long offseason, college football is here. We had a nice appetizer with Week 0, but the first true week of college football is now underway. We have a full slate of games on Saturday, including a number of mouthwatering contests. Ohio State takes on Notre Dame, Arkansas hosts Cincinnati and Oregon meets with Georgia, just to name a few. But look further down the board and you’ll find value on a few games that are off the beaten path.

Let’s look at the three components of our mega parlay for Saturday’s action.

Louisville -5 (-110)

East Carolina +12 (-110)

Southern Mississippi ML (+140)

Parlay odds: +774

Odds available at DraftKings Sportsbook at time of publishing.

For this play we are going with one favorite against the spread and a pair of underdogs; one on the spread and the other on the money line. Let’s break down each of these legs one by one.

Get our college football picks for all of the big Week 1 matchups

Louisville -5 (-110) over Syracuse

To start off our Saturday mega parlay, we’re going with Louisville against the number. The Cardinals bring back one of the best dual-threat quarterbacks in the nation in Malik Cunningham, who should be poised to have a great 2022 campaign. Cunningham rushed for over 1,000 yards and threw for more than 3,000 yards a season ago, including a dominant win over Syracuse. In fact, this matchup has consistently been owned by Louisville of late. The Cardinals seem to have the number of the Orange, with an average margin of victory of 30 points over the last 3 meetings. In fact, Syracuse quarterback Garrett Shrader threw for just 46 yards in the most recent installment. He could be in for another difficult night against a strong Louisville front seven.

Louisville’s middling record last year doesn’t tell the full story. This team was on the wrong side of 4 one-score losses, which could have completely changed the perception of its season. With a healthy Cunningham back in the fold and a defense that returns 6 starters up front, this should be another dominant showing against Syracuse. Back the Cardinals to make a statement in the Carrier Dome.

Be sure to check out our full Louisville Cardinals vs Syracuse Orange predictions

East Carolina +12 (-110) over NC State

It’s easy to see why NC State could challenge for an ACC title this season. This is a team that returns its coach, offensive coordinator and quarterback from a successful 2021 season. Furthermore, the Wolfpack have an excellent defensive unit that can compete with the likes of Clemson. However, they have a tricky game to open the season against East Carolina. The Pirates return quarterback Holton Ahlers, along with some key additions in the transfer portal. East Carolina has one of the best running back rooms in the nation, which should take pressure of Ahlers against this Wolfpack front seven. On the other side, if the Pirates are able to force Devin Leary into obvious passing situations, NC State could have trouble finishing drives. That’s why this number feels a little inflated to me.

NC State could easily win this game by 14+ points. However, I think the situation greatly favors an East Carolina team that is eager to spring an upset. The Pirates ended last season on a 6-2 ATS run, while NC State is just 5-13 ATS in its last 18 road games. With that in mind, I like getting a motivated home underdog at this number.

Be sure to check out our full NC State Wolfpack vs East Carolina Pirates predictions

Southern Mississippi ML (+140) over Liberty

To close out this mega parlay, we’re going with Southern Miss on the money line. Much like Old Dominion on Friday, this Sun Belt team has a real chance to pull off an upset. It starts on the defensive side, as Southern Miss brings back 86% of its defense from 2021, including its top 10 tacklers. The Golden Eagles were adept at creating turnovers a season ago, which bodes well against new Liberty quarterback Charlie Brewer. Brewer struggled at Utah before ultimately transferring, and it won’t be easy for him under center as the Flames lost a big chunk of their offense from last year. Will Liberty be able to generate big plays without Malik Willis? I’m not sure they’ll do so consistently today.

Liberty still likely has the talent edge on paper, but the Flames are also implementing a ton of new personnel in this one. To help our case for an upset, Southern Miss is a team that has a clear identity. The Golden Eagles should start strong on defense, allowing their offense to ease into the game and gain confidence. At +140 or better, I like taking a shot on the Golden Eagles money line to increase our parlay’s value.

Get our CFB Week 1 underdog best bets!

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