#20 Oregon vs. #12 USC Prediction, Spread, NCAAF Picks – Saturday, September 26

This weekend features six exciting college football matchups between ranked teams. This includes #20 Oregon vs.  #12 USC in a Big Ten battle at 7:30 p.m. ET on NBC. According to PrizePicks, Oregon is a 3.5-point favorite on the road.

Oregon is coming off an 84-0 win over FCS program Portland State. USC kicked off its conference schedule last week when it beat Rutgers 42-35.

Let’s dive into our Oregon vs. USC prediction, featuring player projections for college football picks on PrizePicks.

Make your Oregon vs. USC picks on PrizePicks now! 

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#20 Oregon vs. #12 USC Prediction, Spread, Over/Under for Saturday, September 26

All stats are via CFB Stats, PFF, and Games on Paper unless otherwise noted.

Oregon has put itself in a tough situation early in the season. Coming into 2026, the Ducks were ranked #2 in the AP Preseason Poll, and with Oregon QB Dante Moore deciding to return to college instead of entering the NFL Draft, the Ducks were thought of as a national title contender.

Before the first month of the season ended, the country’s perception of Oregon changed. It started with the Ducks' first game, when they nearly lost at home to Boise State. As a result, they slipped from #2 to #6. The Ducks' home loss to Oklahoma State, which they had beaten 69-3 the previous season, dropped their ranking further to #21.

Oregon will have to claw its way back into the top 12 and might need to win the Big Ten championship to do so, and PrizePicks currently gives the Ducks the third-shortest payout to win the Big Ten title (6.25x).

Despite Oregon’s struggles, Moore is playing well this year. He’s fourth in passing TDs (9), sixth in yards per attempt (9.7), and is the only quarterback in the FBS with at least 8 passing TDs and 0 INTs.

Oregon TE Jamari Johnson is questionable after missing the last two games, and backup TE Kendre Harrison is also questionable following an injury in last week’s game vs. Portland State. If either can’t go, it will make it difficult for Moore to work the middle of the field.

The Oregon defense has been disappointing this season, despite some experts expecting it to be among college football's best. In their first two games, the Ducks have allowed 66 points and 828 total yards. 

The Oregon defense must find a solution now against a dangerous USC offense.

The Trojans have scored 39 or more points in all four games. USC QB Jayden Maiava has put himself in the Heisman Trophy conversation, as he leads the country in passing yards (1,173) and passing TDs (12). According to PrizePicks, Maiava has a 16.66x payout to win the award.

USC WR Trent Mosley had a strong start to his season, recording consecutive games with over 100 receiving yards. In the first three games, he led the team in receiving yards (255) and receiving TDs (4). Unfortunately, he is dealing with a knee injury, and after missing last week against Rutgers, he could miss his second straight game.

Fellow USC freshman Kayden Wyatt-Dixon became USC’s go-to receiver in Mosley’s absence, leading the team with 77 receiving yards on 5 catches.

The USC defense was supposed to be revamped under new defensive coordinator Gary Patterson, but it showed weaknesses against Rutgers. The Trojans allowed the Scarlet Knights to post their best offensive performance of the season with 35 points, 460 total yards, and 27 first downs.

Another concern for USC is its track record against Oregon. The Ducks have won four straight games over the Trojans and eight of their last 10.

Oregon vs. USC Spread, Over/Under, Payouts – Saturday, September 26

Oregon comes into Saturday as a 3.5-point favorite vs. USC, per PrizePicks.

Here are the full payouts for Oregon vs. USC on PrizePicks, including winner payouts, the spread, and over/under.

Make your Oregon vs. USC prediction on the over/under on PrizePicks!

PrizePicks data is live at the time of writing and is subject to change.

Oregon vs. USC Prediction on Over/Under – 9/26/26

Here are the key stats and predictions behind our Oregon vs. USC prediction on the over/under for Saturday, September 26.

• USC’s total has gone over in three of four games this season, while Oregon has gone over in all three games.
• The Trojans are among the best at converting on third down, ranking in the 98th percentile for third-down conversion rate (65.2%). The Ducks are in the 97th percentile for opponents’ third-down conversion rate (21.9%), but they have not faced an FBS program ranked in the 50th percentile of the category.
• Oregon is also strong at converting third downs, ranking in the 80th percentile (50.0%). USC has struggled this season, with opponents converting third downs at a 38.1% rate, placing the Trojans in the 45th percentile.
• The Ducks are perfect in the red zone, going 14 for 14, and their 92.3% red-zone touchdown rate is the fourth-best in the nation.
• USC does well at protecting the quarterback, ranking in the 76th percentile for sacks allowed (3.0). Oregon has struggled to generate sacks, ranking in the 44th percentile for sacks (5.0).

Lock in your Oregon vs. USC prediction on PrizePicks before kickoff!

Oregon vs. USC Picks, Player Stats for PrizePicks – 9/26/26

Saturday’s top Oregon vs. USC picks to target on PrizePicks include WR Evan Stewart and QB Jayden Maiava.

Oregon WR Evan Stewart vs. USC: 64.5 Receiving Yards

• Stewart has taken over as the WR1 after Oregon WR Jeremiah McClennon suffered a broken foot.
• Last week against Rutgers, USC's pass defense allowed 15.4 yards per reception, and WR K.J. Duff led the Scarlet Knights with 86 receiving yards. Stewart ranks 33rd in the country with 14.8 yards per reception.
• Stewart is an elusive receiver that has the seventh-most missed tackles in the FBS (6).
• He’s one of the top slot receivers in the nation, ranking 16th in yards per reception when lined up in the slot.

Add Evan Stewart + Oregon to your PrizePicks lineup now.

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USC QB Jayden Maiava vs. Oregon: 266.5 Pass Yards

• Maiava threw for 306 yards against Oregon last season, his fourth-highest total that campaign.
• Maiava has the 10th-most pass attempts in the FBS (115). Oregon ranks in the 22nd percentile in pass attempts allowed per game to FBS opponents (36.0), according to TeamRankings.
• Maiava is 14th nationally in yards per attempt (10.0). That could be trouble for the Ducks, who rank in the 50th percentile in yards per pass attempt (6.5).
• The Heisman hopeful has big-play ability, with his 18 completions of 20+ yards being the most in the country. The Ducks have allowed big plays through the air, ranking 35th in 20+ yard completions allowed (10).

Add Jayden Maiava + USC to your PrizePicks lineup now.

Make Oregon vs. USC Picks on PrizePicks

Oregon’s upset loss to Oklahoma State has put it in a difficult position, and it now needs to show the College Football Playoff committee that it deserves to compete for a national title.

USC’s offense has been explosive to start the season, helping secure its first four wins. The Trojans continue to seek their first Big Ten championship.

Don’t wait until kickoff — make your Oregon vs. USC picks on PrizePicks now. Just pick your players, predict More or Less on their stats, and cash in on your predictions if you’re right. With Team Picks, you can make predictions on game winners, spreads, and over/unders — now available in 36 states!

Keep it here with the Playbook for continued CFB picks, predictions, futures, and more as we jump into the 2026 season.