Northwestern vs USC Pick & Prediction - 11/7/2025
Updated July 9, 2026
The USC Trojans will host the Northwestern Wildcats in Big Ten action in college football on Friday night. The Trojans are heavy favorites on their home turf as they look to remain in the top 25 with a conference win here. Before kickoff from Los Angeles, you can find my breakdown of this matchup, including my Northwestern vs USC prediction.
The USC Trojans are 4-1 in Big Ten play this season and 6-2 overall. They have alternated wins and losses over their last five games. USC bounced back from a 10-point loss to Notre Dame by beating Nebraska in their last game. It was the USC defense that got them through that contest, holding Nebraska to just 17 points. USC will try to repeat that performance on defense here.
Northwestern had an extended winning streak snapped in its last game. The Wildcats lost by a touchdown on the road to Nebraska on October 28 and they will try to bounce back from that loss here. Offensive execution will be the big question mark for Northwestern as they look to upset USC. Northwestern has scored 22 or fewer points in three straight games entering this week and they will likely need more than that to shock USC.
USC's Jayden Maiava is the star attraction at quarterback. Maiava has thrown for 2,315 yards, 15 touchdowns, and five interceptions so far this year. He has found wide receiver Makai Lemon for 776 yards and six touchdowns on 50 catches for Lemon.
Preston Stone is the starting quarterback for Northwestern. Stone has 10 touchdown passes and nine interceptions so far this season. He threw two picks and failed to throw a touchdown pass against Nebraska in the Wildcats' last game and needs to take better care of the football here.
Score Projection: Northwestern 17 – USC 33
Win Probability: Northwestern 18%, USC 82%
My best bet for this matchup from Los Angeles is for the USC Trojans to cover the spread as a home favorite against Northwestern. USC is 4-0 at home so far this season and they should be able to create separation on the scoreboard thanks to the huge advantage in passing offense that they enjoy over Northwestern. I'm expecting another big game from Maiava and for USC to win by more than two touchdowns.
Jay Sanin is the GM and Head of Sports at ATS.io. He has been writing about sports gambling since 2013, handicapping tens of thousands of sporting events. He plays sides and totals aggressively across most sports and is more selective in player prop markets. He does his own modeling across most sports, and his family is jealous of how much time he spends on his precious spreadsheets.
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