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Head coach Jeff Tedford of the Fresno State Bulldogs holds up the championship belt following the LA Bowl as we share our top upset picks for Week 6.
Head coach Jeff Tedford of the Fresno State Bulldogs holds up the championship belt following the LA Bowl. Photo by Kevork Djansezian/Getty Images via AFP.

Unfortunately, four of the five AP Top 25 teams that lost last week were underdogs in their matchups, but we're back with three college football upset picks for Week 6, all based on the best NCAAF odds.

No. 13 Washington State stands out as the lone ranked team playing as an underdog against an unranked opponent this week.

But in our upset picks, we're specifically considering one of the four matchups between AP Top 25 teams, which happens to be one of the biggest rivalries in college football.

Additionally, we're turning our attention to a Big Ten matchup in which the underdog is fortunate enough to face a backup quarterback.

Finally, we're getting a bit bold by banking on the nation’s second-longest winning streak ending this weekend.

To help with your college football predictions for Week 6, here are our best college football upset picks for Week 6 (odds via our best college football betting sites; pick confidence based on a 1-to-5-star scale).

College football upset picks: Week 6

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College football upset predictions

Oklahoma vs. Texas (+172 via FanDuel) ⭐⭐⭐

Texas snapped a four-game losing streak in the Red River Showdown in a big way last year, shutting out Oklahoma 49-0 for its most lopsided win in the history of the rivalry. In addition, the 49 points scored by the Longhorns were their most in the rivalry, which dates back to 1900. However, if one is merely looking at the final score, they would not account for Sooners quarterback Dillon Gabriel missing the game, as he suffered an injury the week prior.

The start of Brent Venables’ tenure in Oklahoma last year was rough, as the Sooners lost three of their first six games for the first time since 2009 and started 0-3 in Big 12 play for the first time since 1998. But Gabriel is back to right the ship, and he entered the season with the second-most career passing yards among FBS quarterbacks while starting the season as one of two FBS quarterbacks with 90-plus career touchdown passes. 

That experience in a game of this magnitude is immeasurable, and an Oklahoma defense that allowed 30 points per game and 461 yards per game last season (the worst ever for a Venables-coached defense) has turned things around, with the fourth-best scoring defense in the country entering this week (10.8 points per game allowed). 

There is no doubt that Texas has its most talented team in the Steve Sarkisian era, but we are getting great value on Oklahoma in what should be a fun atmosphere with the partisan crowd in Dallas. FanDuel is the only sportsbook offering better than +170 odds to back the ‘dogs.

Our Phil Wood dives deeper into this matchup with his Oklahoma vs. Texas predictions.

Purdue vs. Iowa (+120 via DraftKings) ⭐⭐⭐

Iowa is not a quarterback-centric offense, and the Hawkeyes can win games merely on the strength of a stout defense and special teams. However, losing Cade McNamara last week significantly lowers the ceiling of an offense that struggled to score points to begin with, and he is now replaced by Deacon Hill, who entered last week with 49 passing yards on eight attempts.

Purdue is coming off a 25-point drubbing of Illinois, and quarterback Hudson Card had arguably his best game in a Boilermakers uniform. Card finished with a 68.8 QBR and played interception-free football for the third time this season. The Boilermakers are 2-1 in those games and would be 3-0 if not for squandering a late lead with under five minutes to go to Fresno State.

Iowa entered last week ranked 112th or worse in both Passing and Rushing Success, and we do not envision those numbers getting better with a quarterback as inexperienced as Hill, who Purdue has some game film with which to game plan for. While the Hawkeyes defense ranks in the top six of the Big Ten in yards per game and points per game allowed, it is still not a defense built to pressure and harass opposing quarterbacks, as the Hawkeyes entered last week ranked 125th in Havoc. Thus, if Card can play mistake-free football, the Boilermakers should have enough success offensively to pull the upset.

DraftKings offers the best value for Purdue moneyline backers, with the next-closest shop at +118 odds.

Wyoming vs. Fresno State (+185 via DraftKings) ⭐⭐⭐

Our boldest upset pick regarding moneyline odds is Wyoming against Fresno State, as a Cowboys victory would end the Bulldogs’ 14-game winning streak. That streak is the second-longest active streak behind Georgia and the second-longest in school history.

If you have never watched a game played in Laramie, it is must-watch television and was also the site of the Cowboys’ first big upset of the season when they beat Texas Tech 35-33 at home in the season opener. Wyoming’s only loss to this point is a 31-10 defeat against Texas, and the Longhorns have beaten every opponent not named Alabama by a worse score. 

Look for the Cowboys to employ a similar bend-but-don’t-break mentality as it did in the upset of Texas Tech, as the Red Raiders mustered just 20 points from its seven scoring opportunities. Wyoming has mustered just 10 total points in the last four combined matchups with Fresno State, but the Cowboys are a much more formidable offense this year, as evidenced by their top-20 ranking among non-Power Five schools in Stuff Rate.

This is a three-star play, as before the season started, SP+ gave the Bulldogs a 33% chance of losing two or fewer games. Wyoming is one of their toughest remaining games, and we are heading to DraftKings for our wager, as no other sportsbook offers better than +178 odds at the moment.

College football upset picks made 10/2/2023 at 4:13 p.m. ET.

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