The 2025 College Football season rolls on with a full Saturday slate of Week 6 games. Welcome to our CFB Best Bets as we break down CFB picks for this week’s action. Let’s focus on two matchups for our top CFB predictions. Plus, check out more college football bets below.  

Saturday’s Week 6 college football slate lasts all day and all night. That means we have plenty of ways to go for our CFB picks. Note that all bets below are for one unit unless otherwise noted. Without further ado, let’s dive into our CFB Best Bets. 

CFB Picks, Predictions & Best Bets: Week 6 Saturday, 10/4

Let’s kick off Saturday’s Week 6 CFB Best Bets with a Big 12 showdown featuring Iowa State and Cincinnati. Plus, let’s target a total in a Big Ten clash between Illinois and Purdue. Be sure to check out more CFB picks below for other Week 6 games. Good luck!  

 

 


 

Iowa State vs. Cincinnati Prediction: Saturday, October 4th

We have an intriguing Big 12 matchup here with Cincinnati hosting No. 14 Iowa State. Although the Cyclones are the ranked team in this game, they come in as slight road underdogs to the unranked Bearcats. It’s also notable that this spread has flipped to Cincinnati’s side, as Iowa State was previously a 3-point favorite. 

That all should tell us something right away. The sportsbooks are signaling that they have Iowa State and Cincinnati more evenly matched in power ratings than the AP Top 25 rankings may suggest. AP voters see a 5-0 Cyclones squad with wins over Kansas State, Iowa, and Arizona. The Bearcats, though, are a strong 3-1 team and easily could be undefeated themselves. 

In its season opener on a neutral field, Cincy lost by 3 points to Nebraska. The Bearcats nearly came back from a 10-point deficit to tie the game, or even win, but an interception in the end zone with 30 seconds left was the dagger. Cincinnati is coming off an impressive road win at Kansas last week and gets a prime opportunity at home here. 

As for Iowa State, being unscathed through its schedule to this point is hard to ignore. Plus, the Cyclones are riding high after last week’s 25-point home victory over Arizona. Yet, they’ve also been a tad lucky after surviving a pair of one-possession games against Kansas State and Iowa earlier this season. Either or both could’ve been losses, in which case, we’re viewing ISU in a different light. 

Plus, this will be Iowa State’s first conference road test of the season. The Cyclones have played just one other road game and eked out a 24-16 win at Arkansas State. That was essentially a coin-flip contest, which is notable since ISU entered as 21-point favorites. 

In this game, Cincinnati’s offense can set a tone early and make it tough on Iowa State to keep pace. The Bearcats are averaging 39.5 PPG this year (16th in FBS) while putting up 479.5 total yards of offense per game (17th). The offense also ranks 5th nationally in EPA/Play and 10th in success rate. 

Cincy quarterback Brendan Sorsby is playing at a high level right now. He just accounted for 440 total yards in last week’s upset win over Kansas. He also boasts a 10:1 TD:INT ratio with a 180.0 QB rating, while leading a passing attack that ranks 5th in the country in EPA/Pass. 

Iowa State has benefited from playing with a lead or competing in tight, lower-scoring matchups. Thus, the Cyclones’ offense has been able to lean on a strong run game without putting too much pressure on QB Rocco Becht. Well, that won’t be the case this week as Cincinnati’s defense ranks 31st in the FBS in rushing yards allowed per game, and 14th in EPA/Rush. 

If Iowa State is forced to throw more and match Cincinnati in a higher-scoring game, that could be trouble for the Cyclones. Their offense still lacks true playmakers in the receiving corps after losing Jaylin Noel and Jayden Higgins to the NFL this past offseason. ISU’s unproven pass-catchers haven’t needed to do much this year yet, and that could show itself in this road setting. Take Cincinnati to get a statement win at home. 

 

 


 

Illinois vs. Purdue Prediction: Saturday, October 4th

Let’s now focus on an early afternoon Big Ten matchup as Illinois visits Purdue. The home Boilermakers have a real shot at pulling off the upset here, but we’re targeting the over/under. Both offenses can have enough success for this to turn into a higher-scoring contest. 

After getting blown out by Indiana two weeks ago, Illinois bounced back with a 34-32 victory last Saturday. The offense put up 502 total yards with QB Luke Altmyer accounting for 356 total yards and 3 TDs. It was an encouraging rebound performance for a Fighting Illini team that scored 52, 45, and 38 points in its first three games.

Illinois now faces a Purdue defense that’s been torched in the past two games. The Boilermakers gave up 460 total yards and 33 points to USC before allowing 535 total yards and 56 points to Notre Dame. Yes, those are also two good offenses, but Illinois has shown it can take advantage of softer matchups. 

Purdue’s defense ranks 130th in the country in EPA/Play and 116th in defensive success rate. The Boilermakers have struggled against both the pass and run. That’s a problem against a balanced Illini offense that ranks 25th in the FBS in success rate and 35th in EPA/Play.

On the other side, though, Purdue can hang offensively as well. Illinois has faced three power-conference opponents this season, and it struggled defensively in each matchup. The Illini gave up 438 total yards to Duke, 579 to Indiana, and 490 to USC. Last week’s weak defensive effort against the Trojans nearly cost them the win. 

Meanwhile, Purdue moved the ball well in its past two games despite losing both by double digits. The Boilermakers put up 379 total yards against Notre Dame and 357 total yards against USC. Quarterback Ryan Browne has been impressive over the first month of the season. His WR corps features three impact transfers as Nitro Tuggle (Georgia), Michael Jackson III (Georgia/USC), and EJ Horton Jr. (West Virginia) provide some playmaking that the offense lacked last season. 

Let’s take the over for this Big Ten matchup. Illinois and Purdue can easily combine for 60+ points this weekend as the offenses set the tone on both ends. 

 

 


 

Best CFB Prop Bets & Other Picks: Saturday, 10/4

 

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