College Football Upset Predictions & Underdog Picks for Week 5

Jason Ence's NCAAF upset picks are fading "Big Game James" Franklin as Dan Lanning and the Oregon Ducks visit Happy Valley on Saturday night, and much more.

Jason Ence - Contributor at Covers.com
Jason Ence • Betting Analyst
Sep 25, 2025 • 11:33 ET • 4 min read
Oregon Ducks NCAAF Dan Lanning
Photo By - Imagn Images. Oregon Ducks head coach Dan Lanning during a college football game.

This weekend’s college football slate is one of the best of the entire season, and that means plenty of opportunity for close games and surprise victories.

Let’s break down the three games I believe set up for the best upset payouts in our Week 5 underdog predictions and college football picks for Saturday, September 27, featuring the Oregon Ducks. 

CFB Week 5 upset picks

  • Arkansas Arkansas (+146)
  • Oregon Oregon (+138)
  • Mississippi State Mississippi State (+245)

Arkansas Razorbacks

+146 at FanDuel

The Notre Dame Fighting Irish can’t stop giving up points.

Even last week, the Irish got torched time and again by Purdue’s offense, with the Boilermakers scoring 23 first-half points. While the Irish forced four straight punts and an interception in the second half, I don’t think they found some magic elixir at halftime.

The Irish have faced two talented offenses this season, and Miami and Texas A&M combined to score 67 points. They also both beat Notre Dame, and I expect the Arkansas Razorbacks to do the same.

Those offenses were good, but Arkansas can post explosive plays at a rate neither the Canes nor Aggies are capable of. Taylen Green and the Razorbacks can hit home runs both through the air and on the ground, ranking Top 15 in pass explosive rate and Top 30 in run explosive rate. 

The Arkansas defense isn’t good either, but Notre Dame’s passing attack isn’t nearly as good as the run game. The Hogs rank 42nd in success rate, and can get after CJ Carr if they can force some third-and-long situations. 

The Irish will find success on the ground, but their defense will get worn down by the high-tempo Arkansas offense. Throw in the fact the Hogs are ticked off after giving away the game to Memphis last week, and I’ll take them to get the victory in what should be a thoroughly entertaining affair. 

Oregon Ducks

+138 at FanDuel

This is another game that should be an entertaining battle between two extremely talented teams. But there are multiple factors that have me backing the Oregon Ducks to get the upset over the Penn State Nittany Lions.

First is third-down performance. Penn State has struggled on both sides of the ball, ranking 88th in late-down success on defense and 107th on offense. Oregon ranks Top 15 offensively and 30th defensively in those metrics. 

Penn State’s schedule has also been nothing but cupcakes. The Nittany Lions have been favored by 40+ in all three games, so to struggle that much on third down is concerning.

Second is the quarterback play. Penn State has one of the best—if not the best—backfields in college football, but Drew Allar is only 5-7 against ranked opponents. And despite a fairly weak schedule, the Nittany Lions rank 42nd in passing success offensively.

Dante Moore is going to face a Happy Valley environment that will test any quarterback, but he’s done a good job so far this season at getting the ball out quickly when necessary. He’s also got a stellar tight end in Kenyon Sadiq.

But coaching is also key here, and until James Franklin proves he can consistently win big games, I’m betting against him doing so. He’s had 24 chances to beat a Top 10 team in his career, and he’s won only four of those. He’s also 16-27 vs. ranked teams at Penn State. 

Dan Lanning beat him last year in the Big 10 Championship, and he’ll get a massive win on the road here. 

Mississippi State Bulldogs

+245 at FanDuel

One of the best ways to pull off an upset is to have success with the ground game and control the clock, and the Mississippi State Bulldogs have a great opportunity to do just that vs. the Tennessee Volunteers.

The Bulldogs rank fourth in rush success this season, and seven in EPA/rush. The offensive line is providing 3.6 line yards per rush, and just one of eight rushing attempts are being stuffed. It’s a big reason why the offense is averaging 5.3 points per quality opportunity.

But it’s also opening up the play-action game. Mississippi State has posted a very strong explosive run rate, and rank in the top half nationally in passing explosiveness. Staying ahead of the chains has them ranked 21st in third-down success.

The Volunteers have a terrific offense, but the defense has shown flaws. They rank 100th in pass success rate, 88th in rush success rate, and 98th in net EPA/play. They’re also in the bottom half nationally in getting off the field on third down, and are surrendering five points per quality possession.

Mississippi State also has the ability to actually handle Chris Brazzell. The Tennessee receiver is a matchup nightmare due to his height, but the Bulldogs can counter with Kelley Jones, who will give up just one inch to the star wideout.

Tennessee’s stuff rate of 16% won’t get the job done here, and Blake Shapen will connect on enough play-action passes to punish the Vols if they load up the box. Back the Bulldogs to get a huge win as Jeff Lebby knocks off his former boss. 

Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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Jason Ence - Covers
Betting Analyst

Jason has been hooked on football since watching Real Madrid and Manchester United in the 2003 Champions League, and has been betting on the sport for nearly 15 years. He has given soccer gambling and fantasy advice for nearly a decade, writing for sites including Rotowire, SB Nation, and The TwinSpires Edge.

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