I’m backing two favourites and picking one over for this week’s college football best bets.
The pregame narrative: The unbeaten USC Trojans hit the road this week to put their stellar offensive start to the test. Elsewhere, the Louisiana Tech Bulldogs can add some legitimacy to their strong start in a road matchup against the UTEP Miners.
Check out the best college football picks for Week 5, featuring an over/under pick for the BYU Cougars vs. Colorado Buffaloes matchup.
College football picks Week 5
Best bet: USC -6.5 (-110)
It’s a tough ask for No. 21 USC to fly to the Midwest for a noon ET kickoff.
That’s really my only concern with this pick. And to me, that’s not enough of a reason to steer clear.
This will be the fourth consecutive week where the Trojans are alternating between the West Coast and the Midwest. That’s just the reality now for many Big Ten programs.
So far, USC has handled itself just fine.
All four of the Trojans’ games have turned into wins by 14+ points. They’d be 3-1 ATS if not for a 75-yard touchdown in garbage time last week by Michigan State.
Saturday’s road date against No. 23 Illinois will easily be USC’s toughest test yet, but it’s not like all four of its games came against doormats.
USC dominated Michigan State and Purdue, both of whom rank in the top 75 in adjusted EPA per play, according to Game On Paper. Notably, Illinois is 75th on the nose in that metric.
The only real test for the Illini was last week against the now-No. 11 Indiana Hoosiers … and that was a bludgeoning.
Indiana outgained Illinois 579-161 and won by 53 points. In that game, the Illini lost six defensive backs due to injury or ejection. And they were already missing all-conference safety Xavier Scott.
Look for USC to run up a big score off the arm of quarterback Jayden Maiava, who leads the nation in yards per attempt (12.7) and per completion (18.0).
Key stat: USC ranks No. 1 in NCAA Division I in offensive success rate and EPA per play. Illinois is outside the top 35 in both categories.
More NCAAF best bets
BYU/Colorado over 48.5 points (-134): No. 25 BYU has a quarterback with a pristine TD-to-INT ratio and a tailback who’s averaging 8.6 yards per carry. That’ll play.
The Cougars moved on from Jake Retzlaff this offseason but haven’t skipped a beat. They’re 3-0 SU and ATS, averaging north of 40.0 points per game.
BYU’s defence has only allowed 16 points so far. But with a cupcake slate featuring East Carolina, Stanford and Portland State (FCS), that isn’t much to boast about.
I expect the Colorado Buffaloes to put up some points after a terrific showing from QB Kaidon Salter last week. The Liberty transfer was benched in Week 3 but responded well last Saturday, throwing for 304 yards and three TDs on 28 attempts.
Colorado has scored 20+ points in all four of its games. The average total in those matchups was 49.5 points.
Louisiana Tech -3.5 (-110): One way to put yourself on the map as a lesser-known program is to hang tough against a top-tier team. Louisiana Tech did that last earlier this month with a 23-7 loss at No. 4 LSU.
The Bulldogs are 4-0 ATS, with three wins of 10+ points as favourites.
UTEP, in fairness, also has a quality loss, as the saying goes (27-10 at No. 10 Texas). But the Miners followed that up by losing at home last week as -5.5 favourites.
Louisiana Tech has covered or pushed this spread in each of the past three seasons vs. UTEP.
I like where the Bulldogs and their dual-threat quarterback, Blake Baker, are at right now.
College football picks made at 4:30 p.m. on 09/23/2025.
Jordan enjoys writing data-driven game previews and analysis articles — especially for MLB markets or NFL/NBA props. And as a proud Ohio University grad, he’ll always have a soft spot for college sports (especially if the Bobcats are involved). Previous stops include mlb.com, Sportsnet and The Athletic.