College Football Upset Predictions & Underdog Picks for Week 6

Cal has already defied the college football odds twice this season, and Jason Ence expects an encore from the Bears on Saturday night against Duke.

Jason Ence - Contributor at Covers.com
Jason Ence • Betting Analyst
Oct 2, 2025 • 18:54 ET • 4 min read
Jaron-Keawe Sagapolutel Cal Bears NCAAF
Photo By - Imagn Images. California Golden Bears quarterback Jaron-Keawe Sagapolutele (3) rolls out to pass.

Underdogs are doing fairly well this season, and Week 6 of the college football season gives us plenty of opportunities to find value on the money line.

Here are the three college football picks that I'm keying in on to provide the best bang for the buck via an upset.

CFB Week 6 upset picks

Purdue moneyline

+300 at FanDuel

Purdue has had a week to rest up after its loss to Notre Dame, but there were plenty of positives for the Boilermakers to build on coming out of that game. A long weather delay somewhat derailed them, but before that, they were putting up points at a high clip and hanging with the Irish.

It’s the offense that has me backing them to take down Illinois in what should be a high-scoring game. Neither team has a defense that is worth writing home about, but Purdue has actually found ways to hold teams to field goals, which has them sitting Top 30 in points allowed per quality drive.

On offense, they are 21st in quality drive rate and should find plenty of opportunities in the passing game. Meanwhile, Illinois enters the weekend 126th in dropback success rate on defense, 101st in quality drive rate allowed, and 105th in points allowed on those drives. The Boilermakers also rank 26th in available yards gained, an area where the Illini are struggling badly.

Illinois is coming off a thrilling win over USC and has Ohio State next weekend. This is a great look-ahead spot, and Ryan Browne will have a strong outing against their defense as he leads Purdue to victory.

Maryland moneyline

+198 at FanDuel

Washington made four trips to the eastern half of the United States last year as part of the Big Ten, and the Huskies lost all four times. A week after an extremely physical game against Ohio State, they now make the long trek all the way to take on 4-0 Maryland.

The Huskies lost starting left tackle Carver Willis just before halftime, which may lead to a reshuffling of the offensive line in this matchup. That’s problematic, given they have already allowed 12 sacks and have allowed one of the highest pressure rates in college football.

Maryland possesses a strong pass rush, led by Sidney Stewart, who already has 11 pressures and four sacks. Ohio State sacked Demond Williams Jr six times last week and pressured him repeatedly.

Malik Washington has impressed at quarterback, with the Maryland freshman throwing eight touchdowns vs just one interception. While the Huskies are a huge step up in competition, he’s going to find success against a Washington pass defense that is 98th in success rate and 93rd in EPA/pass.

It also helps that Washington’s front seven is quite banged up, with leading pass rusher Zach Durfee likely missing the game. That should give the Terps’ quarterback time to locate Shaleak Knotts. The Maryland wideout is averaging nearly 20 yards a catch and has caught a touchdown in all four games.

Maryland’s defense ranks fifth in EPA/dropback, third in passing success, second in early down success, and third in allowing points per quality drive. The Terps will find success rushing the passer, and the defense will help them move to 5-0 for only the 10th time in their history.

Cal moneyline

+124 at FanDuel

Cal has been the underdog twice this season, and it not only covered but defeated Minnesota and Boston College outright. Now the Bears host an inconsistent Duke team that will be playing well past midnight Eastern on the other side of the country.

Hezekiah Masses presents a serious problem for a Blue Devil offense that has struggled with turnovers. They cleaned things up last week against Syracuse, but Darian Mensah will have to contend with the ACC’s leader in interceptions and pass breakups.

Turnovers have also been an issue for Cal and quarterback Jaron-Keawe Sagapolutele, but last week he went on the road to Boston College and threw for 254 yards and two touchdowns with just one interception. Sagapolutele will face a Duke defense that ranks 112th in quality drive rate, 83rd in points per quality drive, 112th in pass success rate, and 96th in EPA/pass.

It’s difficult for any team to make a trip all the way across the country and perform well, and even more so when that team is prone to making mistakes and being inconsistent. Beating a Syracuse team that lost its starting quarterback against Clemson doesn’t move the needle enough for me.

Cal will force enough turnovers against a fatigued Duke team to get the upset win at home.

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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