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Predictions for 5 must-see college football games in 2021

D.J. Uiagalelei's quote on pressure suggests he'll handle succeeding Trevor Lawrence
Clemson quarterback D.J. Uiagalelei (5) throws the ball during their annual spring game at Memorial Stadium Apr 3, 2021; Clemson, South Carolina, USA.

There are a number of must-see college football games on the schedule for the 2021 season, but several stand out above the rest.

For this list, we’ll look at a Week 1 non-conference showdown between two powerhouse programs, some epic matchups between familiar foes and another underrated Midwestern duel. Oh, and score predictions are included, along with spreads courtesy of DraftKings.

Georgia Bulldogs vs. Clemson Tigers (Week 1)

DateTime (ET)TV
Saturday, Sept. 47:30 PMABC

Taking over for Trevor Lawrence won’t be easy for Clemson quarterback D.J. Uiagalelei, or will it be? As a true freshman last year, Uiagalelei stepped in when Lawrence came down with COVID-19, and threw for 781 yards across two starts, nearly beating Notre Dame before falling in double overtime.

Uiagalelei is obviously the man under center now for the Tigers offense, and should benefit from having a better defense to complement him in 2021.

On the other side, Georgia struggled for continuity last season at QB until JT Daniels asserted himself as the clear starter. Daniels played extremely well down the stretch. Now, we’ll get to see whether that was a flash in the pan or a sign that he could lead the Bulldogs to the College Football Playoff this next year.

Because Georgia lost starting cornerbacks Eric Stokes and Tyson Campbell to the NFL Draft, and Uiagalelei has Daniels beat in terms of sheer arm talent and dual-threat ability, Clemson has to have the edge here in this showdown at Bank of America Stadium in Charlotte.

  • Prediction: Clemson 27, Georgia 24 — Bulldogs (+4) cover spread

Alabama Crimson Tide vs. Florida Gators (Week 3)

Predictions for 5 must-see college football games in 2021
Apr 17, 2021; Tuscaloosa, Alabama, USA; White quarterback Bryce Young (9) scrambles for a first down after moving away from Crimson linebacker Christopher Allen (4) during the Alabama A-Day game at Bryant-Denny Stadium. Mandatory Credit: Gary Cosby-USA TODAY Sports
DateTime (ET)TV
Saturday, Sept. 183:30 PMCBS

Alabama is going to be heavily favored in this contest and in its opener against the Miami Hurricanes. Nevertheless, that’s a lot to put on the shoulders of a young signal-caller in Bryce Young.

Being a successor to two straight first-round NFL QBs in Tua Tagovailoa and Mac Jones is a tall order for Young. He’s also transitioning to a different system under new offensive coordinator Bill O’Brien. He was last seen running the Houston Texans into the ground.

So, this is anything but a slam-dunk road trip for the Crimson Tide as they enter The Swamp in Gainesville. And remember that Nick Saban struggles most against QBs who can make plays with their legs, which is precisely where Florida’s Emory Jones is at his most dangerous.

Jones is unproven and untested as a passer. He’ll have Saban’s complex schemes and insane talent to negotiate. Kyle Pitts would’ve been a big help had he not gone to the pros.

Alabama should win this one, but it shouldn’t be the blowout many oddsmakers project it to be.

  • Prediction: Alabama 35, Florida 24 — Gators (+14.5) cover spread

Cincinnati Bearcats vs. Notre Dame Fighting Irish (Week 5)

Predictions for 5 must-see college football games in 2021
Jan 1, 2021; Atlanta, GA, USA; Cincinnati Bearcats quarterback Desmond Ridder (9) throws a pass against the Georgia Bulldogs in the second quarter of the Chick-fil-A Peach Bowl at Mercedes-Benz Stadium. Mandatory Credit: Brett Davis-USA TODAY Sports
DateTime (ET)TV
Saturday, Oct. 22:30 PMNBC

Notre Dame fans should brace themselves for a down season, because as of right now, the Fighting Irish are only 3.5-point favorites over Cincinnati at home in Week 5.

That’s not to take anything away from the Bearcats, though. They’re returning plenty of players from last year’s exceptional team, including long-tenured QB Desmond Ridder and star cornerback Ahmad Gardner to lead an elite defense.

The Fighting Irish will deploy Wisconsin transfer Jack Coan to lead the offense, and despite a solid year for the Badgers in 2019, he didn’t play this past season.

Coan is facing massive expectations, and isn’t great at escaping the pocket. That’s not great, considering how stout Cincinnati is defensively. More important, Notre Dame lost three offensive line starters to the first three rounds of the 2021 NFL Draft.

A 24-21 loss to Georgia in the Peach Bowl proved this core of Bearcats players could play with the country’s best. They’re going to reinforce that notion when they knock off the Irish in South Bend.

  • Prediction: Cincinnati 28, Notre Dame 21 — Bearcats (+3.5 spread; +123 moneyline)

Ohio State Buckeyes vs. Indiana Hoosiers (Week 8)

Predictions for 5 must-see college football games in 2021
Indiana Hoosiers quarterback Michael Penix Jr. (9) passes as Ohio State Buckeyes defensive tackle Tommy Togiai (72) pressures during the fourth quarter of a NCAA Division I football game between the Ohio State Buckeyes and the Indiana Hoosiers on Saturday, Nov. 21, 2020 at Ohio Stadium in Columbus, Ohio. Credit: Joshua A. Bickel/Columbus Dispatch via Imagn Content Services, LLC
DateTime (ET)TV
Saturday, Oct. 23TBDTBD

The left arm of Michael Penix Jr. absolutely torched the Buckeyes’ secondary in 2020 for 491 yards and five touchdowns. Had he not thrown a pick-six in that 42-35 loss, Indiana may have emerged from the Horseshoe in Columbus with a stunning upset victory.

Penix later went down with a torn ACL, but will be plenty healthy in time for this marquee tilt. Indiana may be known as a basketball school historically. However, the tables have turned of late, and the Hoosiers are a hard-hitting, stout defense with a legit QB to boot.

Indiana forced eventual first-round pick Justin Fields into multiple mistakes the last time these teams met — three interceptions, to be exact. Given Fields’ struggles, how does C.J. Stroud expect to fare? Probably not much better.

The Hoosiers will be playing with an edge on defense, in front of its home fans, and likely have the advantage at the most important position on the field. Sounds like an upset brewing in Bloomington.

  • Prediction: Indiana 35, Ohio State 31 — Hoosiers (+11 spread; +300 moneyline)

Michigan Wolverines vs. Penn State Nittany Lions (Week 11)

Predictions for 5 must-see college football games in 2021
Nov 28, 2020; Ann Arbor, Michigan, USA; Michigan Wolverines head coach Jim Harbaugh on the sideline in the second half against the Penn State Nittany Lions at Michigan Stadium. Mandatory Credit: Rick Osentoski-USA TODAY Sports
DateTime (ET)TV
Saturday, Nov. 13TBDTBD

Not that big things are necessarily expected of Michigan under Jim Harbaugh, but it’s getting to the point where he needs to start delivering in big spots. Otherwise, even his alma mater won’t stick by him much longer.

Penn State struggled through much of 2020, but after losing five straight to start, the Nittany Lions roared back with four consecutive wins.

True freshman J.J. McCarthy is at least pushing Cade McNamara for Michigan’s starting quarterback job, but the latter is more experienced, so Harbaugh is bound to lean on him. Maybe by this point, the season will be lost, and McCarthy will be in anyway. Regardless, plenty of uncertainty there.

Sean Clifford is more of a sure starting field general for the Nittany Lions, whose incredible home-field advantage will loom large in this one. Expect a full white-out crowd ready to rumble as the Wolverines try to hang on and keep this one competitive.

If Michigan plays desperate enough and wins, it’ll reflect well on Harbaugh. On the other hand, should the Wolverines get blown out only two weeks before the big rivalry game against Ohio State, it could really crank up the temperature on Harbaugh’s hot seat.

Nothing about these circumstances is shaping up well for Michigan to hang tough, or even cover a generous spread.

  • Prediction: Penn State 24, Michigan 13 — Nittany Lions (-7.5) cover spread