College Football Best Bets & Predictions for Week 6 Afternoon Games

Week 5's afternoon slate features a pair of big-time SEC showdowns, with Alabama looking to avenge last year's upset to Vanderbilt, while Texas takes on Florida.

We've got a best bet for both of those games, plus a few additional matchups in the late-afternoon time slot — see below for our college football picks and analysis.

College football best bets for Week 6 afternoon games

Game	Time (ET) Network	Best bet
vs	3:00 | TNT	-20.5 -105
vs	3:30 | ABC	+10.5 -110
vs	3:30 | ESPN	-6.5 -120
vs	3:30 | CBS	-24.5 -115
vs	3:30 | NBC	TT o41.5 -115
vs	3:30 | ESPN2	-6.5 -110
vs	3:30 | BTN	u40.5 -108

CFB Week 6  preview with Andrew Caley and Douglas Farmer

College Football Week 6 Preview with Douglas Farmer and @Covers_Caley https://t.co/UIimpovvAN

— Douglas Farmer (@D_Farmer) October 1, 2025

Oklahoma State vs Arizona best bet

Arizona -20.5 (-105 at FanDuel)

Oklahoma State has not been good for a while, having lost 12 straight games to FBS competition, with its only win of the year against UT Martin. Defensively, the Cowboys are last in the Big 12 in surrendering 35 points per game and a whopping 473 yards of offense.

See our full analysis and Cowboys/Wildcats SGP in our Oklahoma State vs. Arizona predictions.

Vanderbilt vs Alabama best bet

Vanderbilt +10.5 (-110 at FanDuel)

Diego Pavia and this Vandy offense are better than the Florida State one that punished 'Bama. The Commodores are also confident; Pavia went on On3 and said, “But we just gotta play within the white lines. If we do that, if we play our game, it won’t be close.”

See our full analysis and Commodores/Crimson Tide SGP in our Vanderbilt vs. Alabama predictions.

Texas vs Florida best bet

Texas -6.5 (-120 at FanDuel)

It feels like Florida keeps getting priced as either: 1) A team finally about to stand up and do something with their head coach’s job on the line, or 2) A team that simply can’t be as bad as what we’ve seen. That was the case against LSU as a 4.5-point underdog, and again against Miami as a 6.5-point underdog. They failed to cover both, and here we are again.

See our full analysis and Longhorns/Gators SGP in our Texas vs. Florida predictions.

Penn State vs UCLA best bet

Penn State -24.5 (-115 at FanDuel)

There are nightmare seasons... and then there’s whatever the UCLA Bruins are experiencing in 2025. After a disastrous 0-4 start, the program has parted ways with its head coach, offensive coordinator, and defensive coordinator. It’s only going from bad to worse with the Penn State Nittany Lions in town, hungry after a loss to Oregon in the national spotlight.

See our full analysis and Nittany Lions/Bruins SGP in our Penn State vs. UCLA predictions.

Boise State vs Notre Dame best bet

Notre Dame team total Over 41.5 (-115 at FanDuel)

The Irish know they need these points; there was a reason Marcus Freeman called a fake punt late in a blowout at Arkansas: More points equal a better Playoff chance. Notre Dame will remain aggressive offensively, defensively, and on special teams well past the usual easing point. That should equal at least six touchdowns.

See our full analysis and Broncos/Fighting Irish SGP in our Boise State vs. Notre Dame predictions.

Virginia vs Louisville best bet

Louisville -6.5 (-110 at FanDuel)

This is a play against Virginia; they're coming off a big win, going on the road, and I'm not sure they're prepared to deal with success, so they're going to fall flat this week.

See more early college football Week 6 picks from the Covers YouTube channel.

UL-Monroe vs Northwestern best bet

Under 40.5 (-108 at FanDuel)

All three of the Wildcats’ home games this year have gone Under their totals, despite a blowout of FCS-level Western Illinois, despite garbage-time touchdowns against Oregon, and despite UCLA’s defensive woes.

See full analysis — and all of Douglas Farmer's best bets this week — in his college football Week 6 predictions.

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