Oregon vs USC Prediction, Picks & Early Odds: College Football Week 4

Want to get more Covers content? Add us as a preferred source on your Google account here.USC will look to stay undefeated when Oregon visits Los Angeles Memorial Stadium on Saturday at 7:30 p.m. ET (NBC). The Ducks are 2.5-point road favorites, and my Oregon vs. USC prediction and college football picks expect Dante Moore & Co. to take advantage of the struggling Trojans defense. Oregon vs USC predictions For help understanding Kalshi probabilities, see our odds calculator. Pick Probability Oregon -2.5 55% Over 62.5 50% Percentages courtesy of Kalshi, one of the best prediction market apps. Early Oregon vs USC spread pick: Oregon -2.5 Kalshi probability: 55% While Oregon has a loss, the Ducks remain the more trustworthy team. USC's defense is one of the worst in the country, and the main reason I like Dan Lanning's team to cover -3.5 or better. The Trojans allowed 460 yards and 35 points to a Rutgers offense that's ranked outside the Top 75 in EPA per pass and EPA per rush. The 7-point win against the Scarlet Knights was the third time in four games this season Lincoln Riley's program failed to cover the spread. USC has played three Group of Six programs and a Rutgers team that's lost to UMass and Boston College... and the Trojans are 1-3 ATS, with a defense ranked 90th in EPA per pass, 107th in EPA per rush, and fourth-worst in the Big Ten in havoc rate (13.5%). And although the Ducks have struggled with injuries and offensive line inconsistencies, Dante Moore still has this offense ranked sixth by SP+. Oregon has scored 31+ in all three of its games, and Moore & Co. could hang 40+ on USC. Our Brad Powers is also laying the points with Oregon in his early Week 4 picks. Start trading with Kalshi today! Sign up now using our exclusive Kalshi promo code 'COVERS60' and trade $25 on any event contracts to get $60 — including college football! Sign Up Now at *Eligible U.S. locations only Early Oregon vs USC total pick: Over 62.5 Kalshi probability: 50% USC's defense hasn't improved under Gary Patterson, and if anything, it's gotten worse. The Trojans rank 98th in early-down EPA per play (a metric Oregon's offense ranks 17th in) and 86th in third/fourth down success. SP+'s average offensive ranking of USC's opponents this year is 89.7, with Rutgers being the highest at 54th. The Ducks are ranked nearly 50 spots higher, with one of the best QBs in the country, and no shortage of playmakers. But the reason Oregon lost to Oklahoma State was its defense, and USC has the talent to take advantage, too. The Ducks are 74th in available yards percentage on defense (47.7%), and their D-line has been a major disappointment, with Oregon sitting 14th in the Big Ten in havoc rate (15.1%). As always, USC's offense is potent under Riley. It's second nationally in available yards percentage (75.8%), and Jayden Maiava is 10th in QBR (87.4) and leads the country in TD passes (12). A shootout is brewing in L.A., and I like the Over at 63.5 or better. Oregon vs USC odds Oregon vs USC spread: Oregon -2.5 Oregon vs USC moneyline: Oregon 59%, USC 41% Oregon vs USC Over/Under: 51.5 How to watch Oregon vs USC Date: Saturday, Sept. 26, 2026, 7:30 p.m. ET City: Los Angeles, Calif. Venue: Los Angeles Memorial Stadium TV: NBC Odds are correct at the time of publishing and are subject to change.Not intended for use in MA.Affiliate Disclosure: Our team of experts has thoroughly researched and handpicked each product that appears on our website. We may receive compensation if you sign up through our links. MORE FREE COLLEGE FOOTBALL PICKSThis article originally appeared on Covers.com, read the full article here and view our best betting sites or check out our top sportsbook promos.