NCAA Football: Arizona State at Michigan State
Mike Carter / USA TODAY Sports

Week 6 of the college football season something of an enigma with four games featuring a pair of AP Top 25 teams. Unlike Week 5, there are few marquee games ripe for upsets. No. 3 Iowa vs. No. 4 Penn State should be a great game, but it's the only matchup featuring a top-10 team playing an opponent within even 10 spots of its ranking. That means it's time to look down the board for upsets. 

Each week, potential upsets are picked based on favorable matchups, context (i.e. location, rivalries, look-ahead games) or just good ol' fashion gut feel. For maximum effect, a spread of at least three points is required for consideration – the bigger, the better. 

Week 5 was exactly what the doctor ordered to move above .500 on the season against the spread behind Boston College, Bowling Green and Kansas State all keeping games close. Of course, my pick of Maryland to beat No. 3 Iowa might be my worst selection yet – the Hawkeyes won 51-14. If it's not my worst pick, thinking No. 13 Arkansas could cover against a supercharged Georgia comes close. 

Still, picking potential upsets is a minefield. We'll take wins wherever we can get them. On to Week 6!  

PicksWeek 5Overall

ATS

3-2

8-7

SU

4-1

6-9

Important disclaimer: "upset" is defined first and foremost by the odds, not rankings. 

No. 13 Arkansas at No. 17 Ole Miss

When: Saturday, 12 p.m. ET | Where: Oxford, Mississippi

The game is in Oxford, but it's difficult for me to understand why Ole Miss is favored by such a lofty number. The Rebels' crowning achievements to this point are dropping 61 points on 1-4 Tulane and jumping on Louisville, which could be looking for a new coach soon. Arkansas was overmatched against No. 2 Georgia – like a lot of other teams would be – but by beating No. 21 Texas and Texas A&M, it showed it could compete with blue-chip talent. It's hard for me to see this game getting out of hand. These two teams are equals. ATS: Arkansas, SU: Arkansas

East Carolina at UCF

When: Saturday, 6 p.m. ET | Where: Orlando, Florida

Don't look now, but East Carolina is quietly 3-2 with wins over Marshall and Tulane. The Pirates' only two losses came against Appalachian State and South Carolina. UCF is fresh off back-to-back losses and headed in the wrong direction without quarterback Dillon Gabriel. And with No. 5 Cincinnati on the schedule in Week 7, this is a classic lookahead spot. The Knights better be careful, otherwise this season could get out of control. ATS: East Carolina, SU: UCF

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Buffalo at Kent State

When: Saturday, 7 p.m. ET | Where: Kent, Ohio

Buffalo has played a difficult schedule featuring matchups against Nebraska, No. 15 Coastal Carolina and an upstart Western Michigan squad that leads all MAC teams in our CBS 130 Rankings. But the Bulls were built to physically bully the MAC and proved it by holding WMU to 3.6 yards per carry. There were high expectations for the Golden Flashes' offense coming into 2021, but they're averaging just 15 points per game against FBS competition. No question, the Bulls can get this done on the road. ATS: Buffalo, SU: Buffalo

Stanford at No. 22 Arizona State

When: Friday, 10:30 p.m. ET | Where: Tempe, Arizona

Stanford is one of the most improved programs since making a quarterback change after Week 1. Tanner McKee is tied with Liberty's Malik Willis for the most touchdowns thrown without an interception. Arizona State ranks among the best rushing teams in the country and Stanford has done a solid job putting together consistent drives. This game could have fewer possessions and be much closer than bookmakers project.  ATS: Stanford, SU: Arizona State

Which college football picks can you make with confidence in Week 6, and which national title contender will go down hard? Visit SportsLine to see which teams will win and cover the spread -- all from a proven computer model that has returned almost $3,400 in profit over the past five-plus seasons -- and find out.