Oregon vs USC Prediction, Pick, College Football Odds for Saturday, September 26

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The Oregon Ducks take on the USC Trojans in Los Angeles on Saturday, Sept. 26. Kickoff is set for 7:30 p.m. ET on NBC.

Oregon is favored by -3.5 points on the spread with a moneyline of -162. USC, meanwhile, comes in as a +3.5 underdog and is +134 on the moneyline to pull off the upset. The over/under sits at 61.5 total points.

Here’s my Oregon vs. USC prediction and college football pick for Saturday, September 26.

My USC vs. Oregon best bet is on the Ducks to cover the spread . Find the best line available on our live NCAAF odds page. For more Week 4 college football picks and analysis, download the Action Network app today.

Oregon vs USC Odds

• Oregon vs USC Spread: Oregon -3.5 (-102), USC +3.5 (-120)
• Oregon vs USC Over/Under: 61.5 (-115o / -105u)
• Oregon vs USC Moneyline: Oregon -162, USC +134

No team needed a get-healthy game more than Oregon in Week 3. An 84-0 demolition of Portland State provided all the statistics a team could want, but the mental health of the roster needed a clear reset.

The Ducks stumbled into the 2026 season with a surprise effort from Boise State. Despite a post-game win expectancy of 99%, Oregon struggled to create space against the Broncos, but the wide receivers did enough in the second half to secure a victory.

The bottom of the boat fell out against Oklahoma State in Week 2, a no-doubt victory for the Pokes. Oregon head coach Dan Lanning admitted mistakes on fourth down, going 0-for-3 on top of a 5-for-14 effort on third down.

The criticism has been justified for an Oregon team expected to compete for a National Championship under two new coordinators. Considered the most experienced defensive line in the country, the Ducks rank 32nd in pass rush and 75th in Stuff Rate.

The offensive line also has room for blame, as quarterback Dante Moore has seen 20 pressures this season . The future NFL signal-caller has seen his pressure-to-sack ratio jump from 16% in 2025 to 30% this season.

If there has been good news, it comes in the secondary.

Cornerbacks Na’eem Offord and Ify Obidegwu have combined for four pass breakups, good enough to place the Ducks at 14th in PFF coverage grading.

With Oklahoma State and quarterback Drew Mestemaker on the schedule, Oregon still ranks as the 15th-best defense in opponent EPA allowed.

Small cracks in the USC box scores turned into a crevasse in Week 3. Playing in their fourth consecutive game, the Trojans hopped time zones with hopes of eliminating past East Coast travel ghosts.

USC traveled to Rutgers in Week 3, facing a team that suffered embarrassing losses to UMass and Boston College earlier in the season.

The Trojans escaped with a one-possession victory, but the defense allowed 460 yards and four touchdowns in five Scarlet Knight trips into the red zone.

Rutgers utilized wide receiver KJ Duff in full. Duff commanded 13 targets and responded by putting up 86 receiving yards and a score.

A couple of key plays kept USC from its first loss, including a 99-yard pick-six by safety Prophet Brown and an early interception that led to a drive starting on the Rutgers 24-yard line.

San Jose State and Louisiana also put points on the board in the Coliseum.

The Spartans averaged six yards per play and scored enough in garbage time to cover the spread.

The Ragin’ Cajuns were a different story, outgaining USC in yards per play with an average of nearly 7.0 while almost posting a touchdown every trip inside the Trojans’ 40-yard line .

The biggest question for Oregon is whether an 84-0 victory over an FCS school is enough to get every player on the same page.

Oklahoma State linebackers identified that Moore was tipping rush or pass plays with his footwork , an issue that was resolved before the Portland State game.

If the Ducks return to full explosiveness on the offensive side of the football, the Trojans’ defense could have a long Saturday.

USC’s defense has regressed under coordinator Gary Patterson, falling outside the top 100 in Passing Success Rate allowed and Pass EPA allowed. The Trojans also sit in the bottom 20 in Havoc, a metric of tackles for loss, sacks, forced fumbles, and passes defensed.

Through four games, the Trojans have generated just seven pass breakups. If those numbers hold true, Moore could have a big passing day with proper fundamentals pre-snap.

Both Evan Stewart and Dakorien Moore have been elite at 2.5 yards per route run , and the loss of Jeremiah McClellan to a broken foot opens the door for a number of blue-chip freshman wide receivers.

USC is sure to get its offensive shots in with quarterback Jayden Maiava, who has already posted a 12:1 touchdown-to-interception ratio.

Despite the big touchdown tally, the senior has seen a dip in big-time throw rate, even with less pressure and fewer drops. Maiava has his worst Success Rate and EPA against quarters coverage , the primary zone look from the Ducks defense this season.

Action Network projects Oregon as a 5.5-point favorite in the Coliseum in Week 4.

There are a number of indicators pointing up, primarily a fix to Moore’s footwork that could hide offensive plays.
The Ducks defense has also been one of the best in the country at limiting explosive passes, an element USC football has relied on to create scoring opportunities.

With the Trojans lacking in rush explosives and Oregon limiting pass explosives, look for the Ducks to be back in the Big Ten — and potentially the national title — picture.

Pick: Oregon -3 or Better

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