College football odds, lines, spreads: Picks, predictions, betting advice for Week 5, 2025 from proven model

The Week 5 college football schedule dives head-first into conference matchups, including a pair of top-15 matchups. Penn State vs. Oregon has the No. 3 Nittany Lions as 3.5-point home favorites over the sixth-ranked Ducks, per the latest Week 5 college football odds. Over in the SEC, LSU vs. Ole Miss sees the No. 4 Tigers as 1.5-point road underdogs versus the 13th-ranked Rebels. Additionally, other ranked matchups feature Georgia vs. Alabama (+2.5) and USC vs. Illinois (+6.5).

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Not every Week 5 college football spread is under a touchdown, as Missouri can attest. The No. 20 Tigers are favored by 44.5 points over UMass in what's the only college football line of the week that's more than 22.5 points. Another game that could be of interest to college football betting is Notre Dame vs. Arkansas (+4.5), which has the highest total of the week at 63.5 (see more college football lines right here). 

Before making any college football picks for those games or others in Week 5, be sure to see what the SportsLine Projection Model has to say. 

The model simulates every FBS game 10,000 times. Since its inception, it has generated a betting profit of well over $2,000 for $100 players on its top-rated college spread football picks, and is a profitable 35-22 combined on money-line and over/under picks since the beginning of 2024. Anyone following could have seen impressive returns.

Now, it has studied the latest college football odds (see the latest college football lines for each matchup this week on our college football odds page), simulated every single play for every Week 5 game, and the results are in. 

One of the college picks the model is high on during Week 5: Washington (+8.5, 52.5) covers versus No. 1 Ohio State in a 3:30 p.m. ET kickoff on Saturday, with the Huskies covering nearly 60% of the time. Another prediction: No. 9 Texas A&M (-6.5, 52.5) covers against Auburn over 50% of the time at Saturday at 3:30 p.m. ET, with the Over hitting more than 50% of the time.

The model has also made the call on who wins and covers in every other FBS matchup, and it's calling for multiple upsets, a shocking result in a ranked matchup!

So which college football teams should you back in Week 5, and which underdogs win outright? ... Join SportsLine now to see who wins and covers every single game, all from the model that has returned well over $2,000 in profit on top-rated ATS picks since its inception!

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