College Football Week 5 Against the Spread Picks for the Biggest Games

The Week 5 college football odds are centered around Tuscaloosa, where No. 2 Georgia will take on No. 4 Alabama in a massive SEC showdown.

We're otherwise dealing with a plethora of double-digit spreads as conference play continues to ramp up. Keep reading for my best college football picks below. 

College football Week 5 picks against the spread

Matchup	Pick
Virginia Tech vs  Miami	-19.5
Kentucky vs  Mississippi	-17.5
Minnesota vs  Michigan	+9
Oklahoma State vs  Kansas State	+4.5
Wisconsin vs  USC	+15.5
Louisville vs  Notre Dame	+6.5
Colorado vs  UCF	-14
Mississippi State vs  Texas	-38.5
Ohio State vs  Michigan State	-24.5
Georgia vs  Alabama	-2
Illinois vs  Penn State	-18
Arizona vs  Utah	+12
Oregon vs  UCLA	+24

Lines courtesy of DraftKings as of 9-24.
Record: 12-10 ATS after Week 4.

CFB Week 5 ATS picks

Virginia Tech vs Miami (-19.5): Miami -19.5

This is admittedly a lot of points against what was expected to be a good Virginia Tech team, but what we've seen from these squads early on is more than enough to justify this spread and then some. Cam Ward has the Canes rolling and that won't change against the Hokies.

Kentucky vs Mississippi (-17.5): Mississippi -17.5

Oh, the curious case of Kentucky — a team that had No. 1 Georgia on the ropes but also lost by 25 points at home to South Carolina. My guess is the Wildcats are closer to the latter, which makes them a team Mississippi should dominate. 

Minnesota vs Michigan (-9): Minnesota +9

The Wolverines were lucky to leave USC with a win considering they got outgained and had just nine second-half yards before the game-winning drive. I'll take the points with Minnesota in what could be a bit of a letdown spot.

Oklahoma State vs Kansas State (-4.5): Oklahoma State +4.5

Week 4 could end up being a turning point for these two programs, with Oklahoma State falling to Utah 22-19 and K-State getting pummeled 38-9 by BYU. Even if Cam Rising didn't play, I'm willing to give the Cowboys more of a pass against what is proving to be the cream of the crop in the Big 12.

Wisconsin vs USC (-15.5): Wisconsin +15.5

The Michigan game was certainly a gut-punch for a USC team that was staring a 3-0 record in the face. A bounce-back win is likely coming against Wisconsin and a backup QB, but the Badgers are coming off a bye and will be just as desperate after losing 42-10 to Alabama in Week 3.

Louisville vs Notre Dame (-6.5): Louisville +6.5

This is an easy decision for me. The Cardinals won't be intimidated by the Irish after beating them 33-20 as a 6.5-point underdog a season ago.

Colorado vs UCF (-14): UCF -14

I can separate my winning choice of Colorado -2 last week from the fact the Buffs needed a last-second Hail Mary touchdown to even give themselves a chance. It's all going to come undone soon and a road game against a much better team (see the Nebraska game) is a good place to start. 

Mississippi State vs Texas (-38.5): Texas -38.5 

The Bulldogs have allowed an average of nearly 460 yards of offense over their last three games, which would place them exactly 124th (out of 134) in the country. This is one of the largest spreads in SEC history but another game of experience for Arch Manning should help propel No. 1 Texas to a 5-0 ATS record.

Okay I was wrong. Two comparable spreads.

LSU -39.5 in 2019 vs Arkansas. Hogs scored 2 TDs in 4th to backdoor.

UGA -39 in 2021 vs Mizzou. Tigers covered by 2 points thanks to goal line stand late in 4th against JT Daniels.

Biggest spread in SEC history is Bama -40.5 vs…

— Jack McGuire (@JackMacCFB) September 23, 2024

Ohio State (-24.5) vs Michigan State: Ohio State -24.5

Ohio State nearly covered last week's 40-point spread despite being particularly sloppy on defense. They also had two successful drives stopped via interception and a 15-yard penalty from Ryan Day. I expect a much tighter performance in the Buckeyes' first Big Ten test.

Georgia (-2) vs Alabama: Georgia -2

Georgia's 34-3 win over what is proving to be a good Clemson team far surpasses anything Alabama has done to this point. The Bulldogs looked vulnerable against Kentucky but I still have way more concerns about this week's opponent. Alabama is not winning this game; it's a hill I'm willing to die on this week.

Illinois vs Penn State (-18): Penn State -18

This is nothing but a bet on Penn State's improved offense. Drew Allar looks confident again and while Illinois should present a solid test, the Illini have yet to face an offense of this caliber. 

Arizona vs Utah (-12): Arizona +12

While concerns about Cam Rising's availability continue to loom over Utah's 4-0 start, Arizona will be coming off a bye and desperate to get back on track after getting smacked by K-State in Week 3. 

Oregon (-24) vs UCLA: UCLA +24

UCLA is far from a good football team but the Bruins did just cover a similar spread on the road against LSU last weekend. I'd have more trust in the Ducks if they were closer to their final form, but such isn't the case. I'll take the 3+ touchdowns at home. 

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