College Football Week 6 Upset Predictions & Picks | Biggest Upsets for Week 6

Last Updated: Oct 7, 2021

I’ve got to admit, spotting upsets (or potential upsets) has become a bit of an obsession.

In a sport as wild and unpredictable as college football, there’s no more satisfying feeling than finding a live underdog and watching it torment a favorite.

Last week, we found another. Arizona State cashed at +145, and we doubled up on the team total as the Sun Devils cruised over 26.5 points. Colorado was a swing and a miss against USC, while Kansas State covered the first half and nearly pulled off the upset against Oklahoma at +350 odds.

Not a bad week overall, but this board has more in store for us.

The Week 6 college football slate is ripe with live underdogs and we’ll kick things off with one of the greatest rivalries in the sport.

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Read Chris Wassel’s Caesars Sportsbook review for more insight and get your welcome bonus below, or continue reading this analysis for our best Week 6 CFB upset bet picks.

CFB Week 6 Upset Predictions

No. 6 Oklahoma vs No. 21 Texas (+3.5)

Before the season began, I bet Texas (+9.5) against Oklahoma. I really liked the hire of head coach Steve Sarkisian, and I thought the offense could revolve around running back Bijan Robinson.

(Side note: I am loving that bet right now.)

More than a month into the season, much of that has come to fruition. Now, it hasn’t come without its bumps, as the the loss to Arkansas was certainly a wakeup call. But beyond that, Texas has played largely solid football this season.

Oklahoma is a fascinating team. While still unbeaten, the Sooners haven’t looked particularly dominant at any point this year. And quarterback Spencer Rattler, once the Heisman favorite, just hasn’t quite looked himself. He’s been accurate, but Oklahoma hasn’t had nearly the same explosiveness as it did on offense last season.

To me, ball control is key in this matchup. With Robinson, I could see Texas dictating tempo and flow. While it would be a minor upset according to the odds, it would be a massive upset for the Longhorns.

Prediction: Texas 35, Oklahoma 31

Oklahoma vs Texas Under 63.5 Total Points (-110) at Caesars

Wager: 1 Unit

While both offenses are mighty capable of scoring points, I like the under quite a bit. The rhythm of this game—and goal of each offense—will likely be more about ball control than anything else.

Texas will lean on Robinson, which will keep the clock moving. And Rattler, who is second nationally in completion percentage, will likely move Oklahoma’s offense down the field in smaller chunks.

The clock will wind down fast and help this game stay under.

Texas Moneyline (+145) at Caesars

Wager: 1 Unit

There’s good value here. Outside of that loss at Arkansas, Texas has played very well. And although Oklahoma’s offense started to come to life against Kansas State last week, I still don’t trust this team.

The Longhorns haven’t won this matchup since 2018. That changes on Saturday.

LSU (+3.5) vs No. 16 Kentucky

The importance of this game for LSU head coach Ed Orgeron cannot be emphasized enough.

Less than two years after winning a national title, there’s a growing sense that he could be fired after this season if things don’t improve. And after Kentucky, LSU’s schedule only gets more difficult.

After losing to Auburn last week, Orgeron needs this game. It certainly won’t be easy though, as the Wildcats are coming off a win over Florida in which they were underdogs by more than a touchdown. While Orgeron might be on the hot seat, Kentucky head coach Mark Stoops has perhaps the most job security in the conference outside of Nick Saban.

The Wildcats rank in the top 20 in total defense, although that unit will be tested against an LSU offense that still has plenty of weapons. While all is not well in Baton Rouge, I believe LSU’s more talented roster will prevail to at least quiet the noise for one week.

Prediction: LSU 28, Kentucky 24

LSU Team Total Over 23.5 Points (-110) at DraftKings

Wager: 1 Unit

Although the rushing offense is still abysmal, LSU has enough weapons to create some explosive plays. Kentucky was able to keep Florida in check, although the Wildcats’ schedule outside of that has been awfully kind.

I don’t see the Tigers dropping a 50-burger, but they will eclipse this reasonable number.

LSU Moneyline (+140) at Caesars

Wager: 1 Unit

This won’t fix things. It feels like we’re heading toward an inevitable decision with Orgeron, but this will not be the game that ultimately makes that decision final.

LSU pulls a mild upset and the hot seat simmers for another week.

Deion Smith, LSU

The LSU offense has plenty of playmakers for quarterback Max Johnson to target in Week 6’s trip to Kentucky. (Image: USA TODAY Sports)

No. 11 Michigan State vs Rutgers (+5)

The point spread is, well, curious.

This game is likely to generate a ton of action in Michigan State’s favor considering the Spartans’ ranking and the unblemished record. Running back Kenneth Walker is the nation’s leading rusher. He’s also the heart and soul of Michigan State, and he should play well once again.

But when you dive into Sparty’s wins, it’s not unreasonable to think that Rutgers can really make this interesting. Michigan State’s best win to date is probably Nebraska, and that was a game the Cornhuskers should have won. After that? It has to be Miami by default.

Last week was not kind to Rutgers as Greg Schiano’s team was blown out 52-13 by Ohio State. But up until that game, the Scarlet Knights had played much better. And although last weekend’s results might skew people’s opinions, this is a live home underdog.

Prediction: Rutgers 24, Michigan State 21

Rutgers Moneyline (+180) at Caesars

Wager: 1 Unit

Yes, this can and will happen. After giving Michigan a scare a few weeks back, Rutgers does that and one better to the Wolverines’ in-state rival.

The Spartans do not have the kind of weapons Ohio State has and the flow of the game should be much different this weekend.

I love the value of +180 in this spot.

Michigan State vs Rutgers Under 24.5 First Half Points (-110) at Caesars

Wager: 1 Unit

In that game against Michigan, Rutgers ultimately lost 20-13 but was able to slow down the Wolverines’ offense after some early success.

I could see a similar outcome this weekend, with both teams struggling on the offensive side of the ball.

Thank you for reading our CFB Week 6 Upset Predictions! For more college football analysis, check out our CFB Week 6 Best Bets!


Adam Kramer

Adam Kramer is an NFL, college football, and gambling analyst for The Game Day. While college football has long been his calling, he’s also covered sports such as boxing, horse racing, and baseball at The Game Day and in other places. He’s also written for Bleacher Report, VSiN, and various other outlets over the past decade-plus.

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