Week 2 of the college football season is upon us, which means it's time to dive into some of the biggest games of the week.
First, we'll start in Ames, Iowa, where the Iowa Hawkeyes will be looking to take the Cy-Hawk Trophy back to Iowa City against the Iowa State Cyclones.
Then, we'll head to SEC Country, where the Ole Miss Rebels attempt to exact revenge on the Kentucky Wildcats after a top-10 upset last season.
Finally, we'll close it out with a ranked Big Ten/SEC matchup, as the Oklahoma Sooners and Michigan Wolverines take the field in a top-20 showdown.
Without further ado, let's dive into my college football predictions and NCAAF picks for Saturday, September 6.
College Football Predictions, Picks
The team logos in the table below represent each of the matchups that Action Network senior writer Collin Wilson is targeting from Saturday's Week 2 slate of games. Click on the team logos for any of the matchups below to navigate to a specific bet discussed in this article.
| Game | Time (ET) | Pick |
|---|---|---|
  | 12 p.m. | |
  | 3:30 p.m. | |
  | 7:30 p.m. | |
Specific betting recommendations come from the sportsbook offering preferred odds as of writing. Always shop for the best price using our NCAAF Odds page, which automatically surfaces the best lines for every game. | ||
Iowa State vs Iowa Prediction
The Iowa Hawkeyes take on the Iowa State Cyclones in Ames, Iowa, on Saturday, Sept. 6. Kickoff is set for 12 p.m. ET on FOX.
Iowa State is favored by 3.5 points on the spread with a moneyline of -175. The Hawkeyes, meanwhile, come in at +145 to pull off the upset and take the Cy-Hawk Trophy back to Iowa City. The total sits at 41.5 points.
Here’s my Iowa vs. Iowa State prediction and college football picks for Saturday, September 6.
Iowa Hawkeyes
The Mark Gronowski era did not start according to plan in Iowa City.
The highly-touted quarterback from South Dakota State started 8-for-15 in his passing career as a Hawkeye, often underthrowing targets and generating no big-time throws.
Offensive coordinator Tim Lester looked for downfield success in the passing game, but running the ball pulled Iowa out of danger against Albany.
An injury to starting running back Kamari Moulton opened the door for redshirt freshman Xavier Williams. Through zone read option with Gronowski, Williams generated 122 rushing yards on 11 attempts.
Iowa will continue to use the ground game as the backbone of the offense, but Gronowski's numbers must improve for the Hawkeyes to take the next step.
The defense met the expectations of previous Iowa teams, producing 14 pressures against Albany's offense.
Edge Max Llewellyn and Brian Allen have been charged with leading the Havoc-minded defense under coordinator Phil Parker.
Albany was unable to create a single methodical or explosive drive, a positive for Iowa defensively heading into the Cy-Hawk rivalry.
Iowa State Cyclones
Iowa State's multiple personnel packages are back after the departure of two explosive wide receivers in Jayden Higgins and Jaylin Noel.
The Cyclones have used a considerable amount of 12, 13 and 14 personnel through two games, but there are a number of offensive numbers left to be desired.
Quarterback Rocco Becht has seen 12 pressures in 26 dropbacks this season, indicating that the offensive line has struggled in protection against Kansas State and South Dakota.
King-sized tight end Benjamin Brahmer leads the way in targets and touchdown catches on the season.
The bigger question remains on the defensive side of the ball in the 3-3-5 stack.
Nose tackle Domonique Orange has been essential in stopping the zone read, but ISU still allowed the Kansas State rushing attack to average 4.7 yards per play.
In a short sample size for 2025, Iowa State has a low 30% Success Rate against teams using outside zone read concepts.
Iowa vs Iowa State Pick
The Iowa offense may need a few games of maturation before a vertical passing attack develops. The good news is the use of inside and outside zone read with Gronowski and a stable of running backs.
Moulton is not expected to be available for Iowa in this game, giving more carries to the explosive Williams against an Iowa State defense that struggles to defend the run.
Iowa State, meanwhile, lost the yards-per-play battle against Kansas State in Ireland.
The Cyclones have a protection issue on the offensive side of the ball. Tackles Tyler Miller and James Neal III have already given up seven pressures on the season, a bad sign against Iowa's edge defenders.
Becht has been careless with the ball, even considering the increase in pressure, producing three fumbles through two games.
The trends point to the road team winning in this series, as the visitor has won the Cy-Hawk Trophy in each of the last five iterations.
Action Network's betting power ratings make Iowa State a favorite by a single point, giving any number over a field goal value to the road team.
Pick: Iowa +3.5 or Better
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Kentucky vs Ole Miss Pick
The Ole Miss Rebels take on the Kentucky Wildcats in Lexington, Kentucky. Kickoff is set for 3:30 p.m. ET on ABC.
Ole Miss is favored by 9.5 points on the spread with a moneyline of -350. The total is set at 50.5 points.
Here’s my Ole Miss vs Kentucky prediction and college football picks for Saturday, September 6, 2025.
Ole Miss Rebels
Head coach Lane Kiffin has a pattern of annihilating Group of 5 competition early in the season, only to have a different performance on the road in the SEC.
Ole Miss dominated Georgia State, as half of the offensive possessions were explosive, averaging more than 10 yards per play.
New signal caller Austin Simmons filled the highlight reel, going 20-for-31 passing with multiple touchdowns in the opening game of the season.
Transfer wide receiver Harrison Wallace III from Penn State generated the most targets while hauling in five catches for 130 yards.
Running back Kewan Lacy recharged an Ole Miss backfield that lost numerous production pieces. The former Missouri running back generated six yards after first contact, posting three touchdowns on just 16 rushing attempts.
Kiffin has new names and faces on the field at the skill positions, but he's still running plenty of inside zone plays with considerable success.
Kentucky Wildcats
Quarterback Zach Calzada returned to Power 4 football after a stint at Incarnate Word.
The opening game for the Wildcats against Toledo was not promising for the former Texas A&M signal caller, failing to produce a touchdown pass or big-time throw.
On 10 of 23 passing, Calzada did not show improvement with decision-making, averaging a length of 3.1 seconds in time to throw metrics.
Kentucky was led once again by the defense in victory over the Rockets.
The rushing attack was stuffed by the Wildcats at a high 42% of attempts, posting only 3.1 yards per play on the ground. Toledo struggled in money downs, converting just eight of 21 attempts on third and fourth down.
After escaping Toledo with a 24-16 win, Kentucky enters the Ole Miss game with a mulligan for the offense.
Ole Miss vs Kentucky Pick
The Rebels have been a completely different team on the road in SEC play over the past two seasons, generally lighting up the scoreboard at home.
Across the past two seasons, Ole Miss has failed to score more than 27 points on the road against Florida, LSU, South Carolina, Mississippi State, Georgia and Alabama.
The box score was not the cleanest for Simmons in the opener against Georgia State. The sophomore posted three Turnover-Worthy Plays and an additional fumble against the Panthers.
Kentucky has continued defensive success in defending the zone read option, the preferred offensive scheme for Kiffin.
While this may be a revenge game from an Ole Miss loss that kept the Rebels out of the playoff last year, look for Kentucky to continue to flex on the Rebels' mistake-prone offense.
Pick: Kentucky +9.5 (Play to +8.5)
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Oklahoma vs Michigan Prediction
The Michigan Wolverines take on the Oklahoma Sooners in Norman, OK. Kickoff is set for 7:30 p.m. ET on ABC.
Oklahoma is favored by -4.5 points on the spread with a moneyline of -198. The total is set at 44.5 points.
Here’s my Michigan vs. Oklahoma prediction and college football picks for Saturday, September 6.
Michigan Wolverines
The opening game for freshman phenom Bryce Underwood ended in victory.
Michigan beat New Mexico despite a few hiccups in areas other than the quarterback position.
Underwood completed 21-of-31 passes (with a touchdown) without recording a mistake. Not only did the freshman pass his opening test, the touch on the football in the passing game is new for fans in Ann Arbor.
Michigan needed to replace bundles of production from last year's team, but it produced enough in the opener against the Lobos.
The Wolverines stuffed 11 of 25 New Mexico rushing attempts, limiting the Lobos to just three yards per play.
The havoc of coordinator Wink Martindale carried over from previous season, as the Wolverines generated nine tackles for loss in an opening statement game.
Oklahoma Sooners
The preseason steam on quarterback John Mateer's arrival in Norman was peak leading up to kickoff, but the rushing statistics didn't meet the expectation. Mateer evaded a pass rush for a 20 yards scramble, but managed just eight yards on the ground from three designed rushing attempts.
A trio of running backs also had issues creating yards, as Tory Blaylock, Xavier Robinson and Jovantae Barnes forced just three missed tackles on 23 rushing attempts. Those are tepid numbers for a Sooners offense that was expected to dominate Illinois State on the ground.
The Oklahoma defense did come to play, allowing just seven first downs in the first game. Illinois State went 1-for-11 on third down attempts with an average distance of 9.5 yards.
Combined with four tackles for loss and two quarterback hurries, the Sooners ended the opening game allowing a minuscule 3.3 yards per play to Illinois State.
Michigan vs Oklahoma Pick
The struggles of Oklahoma on the ground weren't expected, as Illinois State limited the Sooners to 3.5 yards per play on rushing attempts. Oklahoma produced just one rush (on 31 attempts) that went for more than 12 yards.
Mateer was able to air out the ball in long distance passing downs, generating a 45% success rate with an average of 12 yards per attempt. The Sooners dependency on the arm of Mateer — strictly in passing downs — could be a hinderance in Norman during Week 2.
Michigan running back Justice Haynes averaged 5.8 yards after first contact with three touchdowns against New Mexico, but it'll face one of the best defenses in the nation.
Head coach Brent Venables had led the Sooners to be a dominate team against the inside zone read through last season and in Week 1 against Illinois State.
For Michigan to get into scoring position on possessions beyond the 40-yard line, Underwood will need to shed the stigma of a freshman playing in his first hostile environment.
Pick: 1H Under 21.5 or Better
