Louisiana vs. #14 USC Prediction, Spread, NCAAF Picks – Saturday, September 12

For Week 2 of college football, we get what looks like one of the premier programs in the Big Ten taking on a Group of Six team, with the Louisiana Ragin’ Cajuns and USC Trojans kicking off on Saturday, September 12, at 11:00 p.m. ET.

USC is already off to a great start, securing two wins by more than 15 points. Louisiana cruised to an easy 39-7 win in its first game of the year vs. FCS program Lamar. Despite the win, the Ragin' Cajuns are notable underdogs with a 22.22x payout to win tonight, per PrizePicks.

Below, we’ll break down a Louisiana vs. USC prediction and player projections for PrizePicks.

Make your Louisiana vs. USC picks on PrizePicks now! 

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Louisiana vs. USC Prediction, Spread, Over/Under for Week 2

Louisiana is trying to regain the dominance it held in the Sun Belt under former head coach Billy Napier. Current head coach Michael Desormeaux has struggled to match his predecessor's success, finishing three of four seasons with a  6-7 record, paired with a career 0-4 in bowl games.

Desormeaux could be seeking a new job after this season if the Ragin' Cajuns aren’t contenders for the Sun Belt title.

Offensively, they finished in the 77th percentile for rushing yards per game (183.2) last season. However, Louisiana lost its top two rushers, with RB Bill Davis transferring to Virginia Tech and RB Zylan Terry heading to Cincinnati.

It looks like it could be a split backfield once again, with RB Darell Smith getting 10 carries and RB Anthony Regan Jr. reaching 8 in last week’s game against Lamar. 

Louisiana QB Lunch Winfield should also get plenty of opportunities to run the ball, which may help mask his below-average passing ability. Despite facing an inferior opponent last week, Winfield threw 2 INTs and 0 TDs. The junior had turnover issues last season with an 11 to 7 TD-to-INT ratio, and he’s already trending in the wrong direction.

Louisiana could be in serious trouble against this new and improved USC defense. Since 2023, USC has ranked outside the top 10 in its conference for points per game allowed each season.

Last week, the Trojans shut out an opponent for the first time in two years, beating Fresno State 39-0. The week prior, San Jose State scored all 26 points in the fourth quarter, with USC’s second- and third-string players in the game. If the defense can support this talented offense, USC could compete for a championship. 

QB Jayden Maiava is emerging as a Heisman Trophy candidate, ranking second in the nation in passing yards (635) and passing TDs (5) and fifth in completion percentage (88.9%). According to PrizePicks, he's still a long shot with a 16.66x payout to win the Heisman Trophy.

Two true freshmen lead the wide receiver group, as 2026 4-star recruit WR Trent Mosley has become Maiava’s favorite target and has begun his collegiate career with back-to-back games of 100+ receiving yards. Former 4-star WR Kayden Dixon-Wyatt had his first 100+ yard performance last week vs. Fresno State.

All stats via CFB Stats and Games On Paper unless otherwise noted.

Louisiana vs. USC Spread, Over/Under for Week 2 – Saturday, September 12

According to PrizePicks, Louisiana has a 22.22x payout to win outright vs. USC.

• Louisiana to Win: Yes 22.22x | No N/A

Plus, the Trojans are 30.5-point favorites with a 59.6 over/under.

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

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

Louisiana vs. USC Prediction on Over/Under for Week 2 – 9/12/26

Here are the key game stats and trends behind our Louisiana vs. USC prediction on the over/under for the Saturday, September 12 matchup. 

• Under head coach Lincoln Riley, USC has won six of its eight home games by 30 points or more against non-Power Four opponents. Both instances in which the Trojans did not cover the 30-point margin were against San Jose State.
• Louisiana will be without several pass catchers for this matchup. TE Caden Jensen, who led the team with 77 receiving yards last week, is out, as is WR Shelton Sampson Jr. — Louisiana's leading receiver in 2025.
• The Ragin’ Cajuns scored all 4 of their touchdowns on the ground last week; however, the Trojans have allowed only 1 rushing TD over two games this year.
• Louisiana lost three of its last four games against Power Four opponents, including two by 30 or more points.
• The Southern Cal defense has been getting to opponents' quarterbacks, with the third-most sacks this season (6). Last season, Louisiana struggled to keep its quarterback upright and ranked in the 44th percentile for sacks allowed (25).

Lock in your Louisiana vs. USC prediction on PrizePicks before kickoff.

Louisiana vs. USC Picks, Player Stats for PrizePicks: 9/12/26

Here are the top Louisiana vs. USC picks to target on Saturday, September 12. Today’s college football picks for PrizePicks include QB Jayden Maiava and WR Trent Mosley.

USC QB Jayden Maiava vs. Louisiana: 305.5 Pass Yards

• Maiava was named to the 2026 Walter Camp Player of the Year Award watchlist.
• Last week, Maiava threw for 349 yards in just three quarters against Fresno State. Last season, Fresno State allowed the second-fewest passing yards per game (153.8), while Louisiana ranked in the 42nd percentile for passing yards allowed per game (224.1).
• Last season, Maiava posted the nation's second-best EPA per dropback (0.39). Louisiana ranked in the 37th percentile last year for EPA per dropback allowed (0.13).
• The Trojans returned all five starting offensive linemen, who ranked in the 91st percentile for sacks allowed in 2025 (15). Louisiana ranked in the 38th percentile for sacks generated last season (23).

Add Jayden Maiava to your PrizePicks lineup now.

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USC WR Trent Mosley vs. Louisiana: 63.5 Receiving Yards

• Mosley ranks second in the nation in receptions (12) and receiving yards (222).
• He also has great hands, as he is one of only six wide receivers in the FBS with at least 14 targets and 0 drops.
• Louisiana CB Maurion Eleam will likely cover Mosley. Last season, Eleam’s worst PFF Defensive Grade came against Louisiana’s only Power Four opponent, Missouri (57.7).
• The true freshman is poised to be one of the country’s most explosive receivers, with the second-most receptions of 20+ yards (4). Last season, the Ragin’ Cajuns ranked in the 33rd percentile for receptions of 20+ yards (41) allowed.

Add Trent Mosley to your PrizePicks lineup now.

Make Louisiana vs. USC Picks for Week 2 on PrizePicks

It feels good to have college football back, and we are already watching the top programs separate from the pack. That includes USC, which has already had two dominant wins. The Trojans have their final game against a Group of Six program on Saturday night before conference play begins.

Don’t wait until kickoff — make your Louisiana vs. USC picks on PrizePicks now and earn real money if you’re right.

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