Week 5 of the 2025 college football season is here and our VSiN team is attacking it relentlessly. If you haven’t already, make sure you check out the Week 5 CFB Betting Hub for write-ups and picks from all of our talented analysts. However, I’d love for you to keep reading for my college football best bets and predictions for this exciting Week 5 slate. I’ll probably add some picks as lines move and more information comes out later in the week — and on game day. If I do, I’ll put them on the VSiN Pro Picks page. Don’t miss out on those.
MORE: Check out our Pro Picks page for college football best bets from all of our analysts
Louisville Cardinals at Pittsburgh Panthers – 12:00 pm ET
Not much separates Louisville and Pittsburgh on the defensive side of the ball. The Cardinals have an Adjusted EPA per play allowed of -0.23 while the Panthers are at -0.13. Meanwhile, Pitt has a slight edge when looking at offense, as the Panthers have an Adjusted EPA per play of +0.03 while the Cardinals are -0.08.
These are just two evenly-matched teams, making it hard to believe the home squad is catching 4.5. Also, under Pat Narduzzi, Pittsburgh is 6-0 against the spread in home games after having been outrushed by 125+ yards in their previous game. The Panthers have won those games by an average of 13.5 points per game. The Panthers are also 13-8 straight-up and 14-7 ATS when coming off a bye week under Narduzzi, so they should be able to capitalize on the extra time to prepare.
Louisville is also just 5-9 ATS as a favorite of 3.5 to 10 points under Jeff Brohm, and the team is also 1-5 ATS as a road favorite in that span. I’ll also add that Miller Moss really struggled in road games last season, with USC going winless away from home during the 2024 season. Well, this might not be a Big Ten atmosphere, but this student section is going to be loud. That’ll make a tough matchup even tougher. And it could be especially tough with Pitt being 28th in the nation in EPA per play against (-0.142) on early-down plays. If the Cardinals can’t consistently put Moss in good third-down situations, he’s going to be in for a rough day.
Bet: Pittsburgh +4.5 (-110 – 1.5 units) & Pittsburgh ML (+155 – 0.5 units)
LSU Tigers at Ole Miss Rebels – 3:30 pm ET
Check out my LSU vs. Ole Miss betting preview for my thoughts on how this game will go!
Bet: LSU ML (+102)
Oregon Ducks at Penn State Nittany Lions – 7:30 pm ET
Check out my Oregon vs. Penn State betting preview for my thoughts on how this game will go!
Bet: Penn State -3 (-123)
Alabama Crimson Tide at Georgia Bulldogs – 7:30 pm ET
Check out my Alabama vs. Georgia betting preview for my thoughts on how this game will go!
Bet: Alabama +3 (-110)
Added Plays
PARLAY: Florida State ML vs. Virginia & Arizona State Alt +8.5 vs. TCU (-139 – 1.5 units)
Notre Dame vs. Arkansas Over 64.5 (-105)
Washington +9.5 (-110 – 1.5 units) & ML (+270 – 0.5 units) vs. Ohio State
PARLAY: Texas A&M ML vs. Auburn & BYU ML vs. Colorado (+107 – 1.5 units)
Check the Pro Picks page for any additional plays, or come back here right before kick-off to see if I added something on the game you’re interested in.
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2025 Record: 18-7 (+12.85 units)
