USC vs Colorado Odds, Picks, and Predictions: Trojans Invade Buffalo Territory

Coming off their first loss this season, Coach Prime and the Colorado Buffaloes return home tonight to the confines of Boulder. The sledding doesn’t get any easier in Week 5 as the undefeated USC Trojans and Heisman Trophy odds favorite Caleb Williams come to town.

Looking at the college football odds, the Trojans are favored to win by at least three touchdowns at -21.5. The line has moved after they opened as 27.5-point favorites at the start of the week. 

It was a nice story for a few weeks, but the fairytale is over for Colorado. With question marks up and down the roster after a blowout loss to Oregon in Week 4, there's no reprieve on Saturday as USC’s No. 1-scoring offense is primed to do some serious damage. 

Read on for my best bet and full college football picks for USC vs. Colorado on Saturday, September 30, and also check out our USC vs. Colorado prop picks for more great bets! 

USC vs Colorado best odds

USC vs Colorado picks and predictions

The luster around this Colorado Buffaloes team dimmed a bit in Week 4 as the Buffs came crashing down to Earth at the hands of Oregon in a 42-6 road defeat. Colorado didn’t reach the end zone until garbage time and mustered just 199 total yards on 3.4 yards per play while the defense was gashed for 522 total yards on 7.2 yards per play. 

After a torrid start to the year, Colorado seems to have been drawn back closer to preseason expectations. This is likely not going to be a team within the top half of the country going forward as there are massive liabilities on the roster despite the top-end talent at a couple of positions.

Oregon is a very tough opponent, sure — but so are the USC Trojans. Lincoln Riley’s squad is undefeated while outgaining its opponents by 204.8 yards per game and 3.9 yards per play. 

It should come as no surprise that the Trojans have been elite on offense again this season. They lead the nation with 55 points per game and yards per play (9.2) and rank third with 569.3 total yards per game. There’s no other way to say it — this is about as good of an offense as you'll see at the college level. 

The Trojans have had a cakewalk of a schedule, however, as this will mark their biggest test of the season to date. Although the defense has looked improved for much of the year (53rd in EPA per play, 32nd in success rate), it showed vulnerabilities last week as lowly Arizona State gained 21 first downs — just one shy of the Trojans.

Colorado averages 5.7 yards per play offensively led by Shedeur Sanders at quarterback, who has completed 76.9% of his passes for 1,410 yards, 11 touchdowns, and just one interception.

Leading receiver Xavier Weaver (461 receiving yards, two touchdowns) is considered questionable after getting banged up and exiting last week’s game late. Travis Hunter is still expected to be on the shelf, leaving the Buffs without one of its top receivers and its top cornerback in one fell swoop. 

The clear mismatch in this game, however, will be USC’s offense against Colorado’s defense. The Buffaloes have been absolutely gashed in their two games against good competition — TCU went for 45 points on 541 total yards and 6.8 yards per play in the opener, while Oregon exploded for 42 points on 522 total yards and 7.2 yards per play a week ago. One can easily fathom USC putting up the biggest fireworks show to date in Week 5. 

The Trojans should be able to do whatever they want offensively. They rank second in both EPA per play and success rate, while Colorado checks in at 119th in EPA per play and 126th in success rate on defense.

The rushing attack (second in EPA per rush, second in rushing success rate) led by South Carolina transfer Marshawn Lloyd should consistently churn out chunk yardage against a bad Colorado defensive front that ranks 114th in EPA per rush, 100th in rushing success rate, and 106th in rushing explosiveness. 

Factor in that a Travis Hunter-less secondary will be hopeless in defending this talent group of USC’s pass-catchers that happens to have the Heisman winner throwing them the football, and this one could get ugly for a second straight week.

USC’s team total is set at 48.5 for Saturday — a mark that it's cleared in three of four games. I see no reason that it would slow down here against a woeful Colorado defense without its best player. 

My best bet: USC team total Over 48 (-110 at bet365)
Picks made at time of writing may not reflect live odds.

USC vs Colorado same-game parlay

USC TT Over 48.5 (-111)

Marshawn Lloyd Over 80.5 rushing yards (-114)

Marshawn Lloyd anytime TD (-370)

+242 +363 at FanDuel

This SGP is a correlated three-legger surrounding USC’s offense. If the Trojans are to put up a lot of points, I’d imagine it’s a productive day for running back Marshawn Lloyd, who seems to have taken over the lead-back role as the most productive rusher for an offense that's going to be scoring a ton of points again this season. 

Last week, Oregon ran for 240 yards on 6.3 yards per rush. TCU went wild for 262 rushing yards on 7.1 yards per rush in Week 1. Heck, even Nebraska compiled 222 rushing yards in Week 2. Lloyd had his biggest game of the season last week against Arizona State, handling 14 carries to Austin Jones’ three and exploding for 154 rushing yards.

This is a very soft matchup and he should surpass this prop with ease as long as he's kept on the field and this doesn't become a blowout early. Colorado is a Bottom-10 team defending the rush and if USC is doing a lot of scoring, it’s likely that Lloyd will get a chance to contribute.

You can squeeze even more value out of this SGP as well by taking advantage of FanDuel's 50% profit boost (applicable to any single bet or SGP in this game), which boosts this wager from +242 to +363.

Learn how to bet a same-game parlay with these helpful tips and strategies.

USC vs Colorado spread and Over/Under analysis

There has been some wild line movement since this line opened at USC -27.5. There has been a wave of action on the underdog, pushing the number down to USC -21.5 at current. The total is set at 73.5 across most books although 74.5 is also available. 

The Buffaloes have been entirely reliant on the passing attack, possessing the highest passing rate in the nation. That makes this a not-so-great matchup as USC had defended the pass well this season (20th in EPA per pass, 10th in passing success rate) and is led by Calen Bullock, one of the best over-the-top coverage safeties in the country. 

Where the Trojans are vulnerable is in the run game, where they rank 123rd in EPA per rush and 126th in rushing explosiveness. It’s unfortunate for the Buffaloes that they're completely devoid of a rushing attack, ranking second last in rushing yards per game (55.8) and yards per rush (1.9) while checking in at 128th in EPA per rush and 126th in rushing success rate — woof! 

The offensive line will be overmatched here as they rank 116th in front seven Havoc and 122nd in power success rate. The strength of USC's defense is up front, where transfers like Solomon Byrd (7.5 TFLs, 4.5 sacks), Jamil Muhammad (5 TFLS, 3 sacks), and Bear Alexander (team-leading 10 hurries, 15 pressures) are making a significant impact.

USC ranks third in Pro Football Focus’ pass-rush grade and should be able to consistently bother Sanders after he was sacked seven times by the Ducks a week ago. 

At this point, I don’t have a ton of faith in Colorado to score points, but the Buffaloes do operate an up-tempo scheme under offensive coordinator Sean Lewis and could be able to contribute to the total considering they’re playing at home. The injuries at wide receiver scare me, especially if Weaver is unable to go considering he’s been Sanders’ go-to target. 

I lean toward USC on the spread, although the line movement is understandable considering last week’s underwhelming performance and the fact this is the second of a tough two-game traveling stretch. The Trojans are still the vastly superior team but will need the defense to pressure Sanders repeatedly to make up for its tackling deficiencies. 

USC vs Colorado betting trend to know

USC is 11-1 to the Over in its last 12 games. Find more college football betting trends for USC vs. Colorado.

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