College Football Week 2 Upset Predictions & Picks | Biggest Upsets for Week 2

Last Updated: Sep 10, 2021

Pace yourselves.

We’re just getting started.

That said, you know the drill. Things can get weird in a hurry in college football. Week 1 of the CFB season certainly showed us that, and Week 2 has a chance to deliver yet again.

You want rivalries? I give you Iowa-Iowa State. You want key out-of-conference games? Allow me to present you Ohio State-Oregon.

It’s not the deepest slate of games we will see all year, but it is still ripe with possibilities.

So let’s get to them, zeroing in on some upsets to be mindful of. Here are some on the horizon.

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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 2 CFB upset bet picks.

CFB Week 2 Upset Predictions

#10 Iowa (+4.5) vs. #9 Iowa State

It’s the best game of the weekend and one of the biggest rivalries in college football. Iowa-Iowa State is also the only game on the docket featuring two teams currently ranked inside the top 10 of the AP Poll.

After Iowa dismantled Indiana in its opener, the Hawkeyes are still catching four-and-a-half points. It’s an intriguing line, although after Iowa State struggled in its opener against Northern Iowa, the Hawkeyes are plenty live.

The series often produces plenty of weird moments, and this could be another. Still, it’s hard to find better value than this on the board.

Prediction: Iowa 27, Iowa State 24

Iowa Moneyline (+165) at Caesars

Tyler Goodson is one of the best running backs in the country many fans have never heard of. He’s also one of the most explosive offensive players—non-tight end edition—that the Hawkeyes have had in some time.

The game will feature more points than expected, and there’s a good chance that Iowa will be on the right end of those points. After a dominant Week 1, it’s hard not to love the value of +165 with the Hawkeyes.

Iowa-Iowa State Over 46.5 Points (-110) at DraftKings

About those points I mentioned. The assumption is that this game will be a meat grinder of a football game. It typically is. Although, in this instance, I actually believe some of the skill position talent mentioned above will ultimately thrive.

Granted, this won’t be a basketball score. But look for Iowa and Iowa State to eclipse 50 points and surpass all reasonable scoreboard expectations.

For a more in-depth look at this game, check out Iowa vs. Iowa State Predictions Week 2.

East Carolina (+2) vs. South Carolina

It’s an obscure game with an obscure line. While the reputation of the SEC doesn’t exactly intersect with a matchup of this nature, it doesn’t quite matter.

The line movement between East Carolina and South Carolina has been fascinating. While the game has changed favorites throughout the week, the Gamecocks have assumed the role as the favorite as the line has matured.

That said, I like the underdog. Yes, it’s a small dog. But still, East Carolina has been showing improvement after being one of CFB’s doormats, and I expect that trend to take a sizable leap forward.

Prediction: East Carolina 24, South Carolina 23

East Carolina Moneyline (+105) at Caesars

South Carolina is starting a quarterback, Zeb Noland, who was a grad assistant not too long ago. He has since, due to injury, been thrust into action. That is a wonderful story, although gambling doesn’t know or appreciate good storylines.

While the Pirates lost their opener to Appalachian State, the Mountaineers are a talented team. I don’t chalk this up as a bad loss, especially when the game was largely competitive. Look for East Carolina to pull the (mild) upset.

In this instance, I’ll take the extra juice on the money line vs. the two points.

East Carolina-South Carolina Under 56.5 Points (-110) at DraftKings

This total is just too high for me. While neither defense is a brick wall, there is still a lot to be learned about these two QBs and offenses.

If the game is going to go by the script presented—a close, hard-fought East Carolina victory—I expect the scoring to be somewhat tame.

Tyler Snead, WR, East Carolina Pirates

Even though they are a small underdog, East Carolina is still one of our CFB Week 2 upset picks against South Carolina. (Image: USA TODAY)

Navy (+6) vs. Air Force

The box score from Navy’s Week 1 game was not pretty. Perhaps that’s being a bit too kind.

The Midshipmen allowed 49 points, scored seven points, and threw for only 61 yards. The last part isn’t necessarily shocking. However, they did average more than four yards per carry and still accumulated nearly 400 yards on offense.

That is not meant to excuse a woeful debut. It is merely acknowledging that maybe, just maybe, the outcome wasn’t as bad as the score says.

This point spread speaks to that. And while Air Force cruised in its opener, it did so against the Lafayette Leopards.

Translation: It’ll be much tougher sledding this time around.

Prediction: Navy 20, Air Force 14

Navy Moneyline (+190) at Caesars

I love the value. It’s the perfect spot to take a stab after a woeful opener.

More than anything, however, I think Navy’s style of play can help control the clock, keep the game close, and generate an upset not many see coming. It’s been a weird stretch for Navy, but for one week, it gets back on track.

Navy-Air Force Under 40.5 Points (-105) at DraftKings

Now, this is a total.

It’s barely over 40 points, which is something we rarely see in today’s scoring-friendly football.

But it also, once again, speaks to the kind of game we are likely to have. And with two teams that are likely to drain the clock with their drives, a very low total is in jeopardy here.

Want to place more bets on upcoming games? Check out our following College Football Picks of the Day:


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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