Updated USC vs. Oregon Betting Odds Highlight Dramatic Shift Since Preseason

After a narrow escape in Week 3, No. 12 USC Trojans will be back at home in Week 4 and host longtime rival No. 20 Oregon Ducks (Sept. 26).

Oregon head coach Dan Lanning, left, and USC head coach Lincoln Riley shake hands before the game as the Oregon Ducks host the USC Trojans on Nov. 22, 2025, at Autzen Stadium in Eugene, Oregon. | USA TODAY Network via Reuters Connect

It's been a tale of two different teams in week 3 for the No. 12 USC Trojans and No. 20 Oregon Ducks. After getting upset by Oklahoma State the previous week, the Ducks got back on track with a dominant 84-0 win over Portland State. For the Trojans, the winless Scarlet Knights of Rutgers took them to the wire in a back in forth battle. In the end it was USC that escaped New Jersey with a 42-35 victory.

During the summer, Oregon opened up as 5.5-point favorites, but that line has since shifted. Before USC’s narrow win, they found themselves as 1.5-point underdogs in early sportsbook odds (Sept. 16). With both squads coming off recent shaky performances, the odds for the Week 4 matchup remain close. According to DraftKings, Oregon is favored by 2.5 points over USC.

Underdogs at Home but a Projected Close Battle

Nov 22, 2025; Eugene, Oregon, USA; Southern California Trojans head coach Lincoln Riley and Oregon Ducks head coach Dan Lanning greet each other after the game at Autzen Stadium. Mandatory Credit: Troy Wayrynen-Imagn Images | IMAGN IMAGES via Reuters Connect

ESPN Analytic’s matchup predictor is giving Oregon the edge with 54.1 percent chance to win. Kalshi is also projecting a Oregon win, giving them 52 percent chance to win. DraftKings is riding with the Ducks, listing their moneyline at -122, +102 for the Trojans. FanDuel also has Southern Cal as underdogs at +106 while Oregon moneyline is currently at -128.

The underdog trend for USC continues at BetMGM with USC moneyline at +105 and -125 for Oregon.

Caesars and Fanatics Sports & Casino have yet to post their odds on the game, but Fanatics Markets has 55 percent of its traders favoring the Ducks in the game, 47 percent choosing the Trojans.

Over/Under and Points Spread

Oregon wide receiver Malik Benson carries the ball amid a tackle from USC safety Christian Pierce as the Oregon Ducks host the USC Trojans on Nov. 22, 2025, at Autzen Stadium in Eugene, Oregon. | USA TODAY Network via Reuters Connect

DraftKings currently has the total points set at 62.5 with USC hitting the under at -110. They’re also giving Southern Cal +1.5 points with -105 odds to cover. FanDuel also has 62.5 total points with the USC under listed at -110, but are giving the Trojans +2.5 points (-110 to cover the spread).

50 percent of Kalshi traders have Oregon to win by 2.5 points while 54 percent of their traders is riding with the over for points scored (61.5).

Per Team Rankings, USC is now 1-3 against the spread (-7.4 ATS). They have been favored in all four games but have only covered 25 percent of the time. Even though its early in the season, they are still 1-2 after a win and while playing at home.

Oddsmakers have consistently inflated the point spreads due in large part in their belief of the Trojans offense, who, in their defense, have scored a total of 172 points through four games (nearly 40-plus points scored per game). While USC’s offense has its own problems, its unfortunately their defense that hasn’t done their share – 46 total points allowed in the second halves of Weeks 0 and 2, now giving up 35 points to Rutgers.

All-Time Records

Oregon defensive lineman A'Mauri Washington blocks a pass by USC quarterback Jayden Maiava as the Oregon Ducks host the USC Trojans on Nov. 22, 2025, at Autzen Stadium in Eugene, Oregon. | USA TODAY Network via Reuters Connect

For those who let history play a factor in their betting:

• USC leads the all-time record 38-24-2 with a all-time home record of 24-11-1.
• Oregon is 8-2 in the last 10 meetings and is currently on a four game win streak. Their most recent win was last season (Nov. 22, 2025) – 42-27.
• The last time USC defeated Oregon at the Coliseum was on Nov. 5, 2026 with a final score of 45-20.
• Lincoln Riley is 0-2 versus Dan Lanning and is 6-13 against ranked opponents.
• USC is currently on a 10-game winning streak at home.

The game is slated for Sept. 26 at 4:30 p.m. PST on NBC.

Game odds refresh periodically and are subject to change. If you or someone you know has a gambling problem and wants help, call 1-800-GAMBLER.

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