Louisville vs South Florida Best Bets, Odds and Betting Splits

• Louisville is a 4.5-point favorite over South Florida in East Region action on Thursday at the NCAA Tournament
• The Bulls enter play riding an 11-game winning streak
• Keep reading for my Louisville vs South Florida best bets, plus odds and betting splits for the Round of 64 matchup

Thursday marks the start of the Round of 64 at the NCAA Tournament, with one of the first games tipping off pitting No. 6 Louisville vs No. 11 South Florida in the East Region.

Online sportsbooks are siding with the Cardinals in the college basketball odds, despite the fact that the Bulls enter play riding a massive 11-game winning streak after claiming the AAC regular-season and tournament titles.

Tip-off is scheduled for 1:30 PM ET on Thursday, March 19, with the game broadcast live on TNT from the KeyBank Center in Buffalo, NY.

Keep reading for my Louisville vs South Florida best bets, plus odds and betting splits for this March Madness showdown.

Louisville vs South Florida Best Bets

• Louisville -4.5 (-118 at BetMGM)
• Under 165.5 (-110 at Bet365)

The storylines leading into this matchup are electric. South Florida guard Wes Enis recently went viral, boldly declaring that the 11-seed is simply the better basketball team. Meanwhile, Louisville is navigating significant March Madness injuries, with star freshman guard Mikel Brown jr listed as day-to-day with a back injury that kept him out of the ACC Tournament.

Louisville vs South Florida Stats

On paper, the numbers view this matchup as highly competitive, with South Florida actually holding an edge in the NET rankings. However, diving into the strength of schedule reveals the biggest mismatch of the game: battle-tested experience. Louisville has run a much more punishing gauntlet. The ACC powerhouse boasts a notably higher SOS, anchored by an Opponents’ Opponent Winning Percentage that heavily outweighs South Florida’s mark.

Louisville has played 20 total games against Top-100 competition this season, logging a 10-10 record against teams in the printable March Madness bracket. Furthermore, they are a flawless 13-0 straight up against teams ranked 101 or lower, meaning they unequivocally take care of business when heavily favored.

Conversely, South Florida has built a shiny 24-8 record by feasting on lower-tier programs, securing 18 of those wins against teams ranked outside the Top 100. Back the favorite to put their opponent away down the stretch and cover the modest spread.

In addition to betting the Cardinals against the spread, I am also taking the under. A full-game total of 165.5 is exceptionally high for a pressure-packed postseason clash. The first-half total is sitting at 77.5, which implies that oddsmakers are banking on an enormous 88-point second half to clear the full-game number. Postseason basketball traditionally tightens up in the final ten minutes as teams prioritize defensive stops and clock management. This game profiles heavily as a physical, grind-it-out affair, where points are at a premium

Louisville vs South Florida Odds

Odds as of March 17, 2026. New Customers can claim the BetMGM Promo Code to bet on March Madness.

As of Tuesday night, the best place to back Louisville against the spread is at BetMGM. They’re hanging a -4.5-point line on the Cardinals at -118 odds, while most other books are a point higher.

If you want to bet the under, make sure you visit Bet365. Their total is listed a full point higher than the rest of the market at 165.5.

BETMGM SPORTSBOOK

Offer

T&Cs

Get Up To $1,500 Paid Back in Bonus Bets

Gambling problem? Call 1-800-GAMBLER (Available in the US), Call 877-8-HOPENY or text HOPENY (467369) (NY), Call 1-800-327-5050 (MA), 1-800-NEXT-STEP (AZ), 1-800-BETS-OFF (IA), 1-800-981-0023 (PR). 21+ only. Please Gamble Responsibly. See BetMGM.com for Terms. First Bet Offer for new customers only (if applicable). Subject to eligibility requirements. Bonus bets are non-withdrawable. In partnership with Kansas Crossing Casino and Hotel. This promotional offer is not available in DC, MS, NY, NV, ON, or PR.

LOCK IN PROMO

CODE: SBD1500

CODE: SBD1500

SIGNUP BONUS

GET UP TO
$1,500 BACK

IN BONUS BETS!

BET NOW

Louisville vs South Florida Betting Splits

Moving over to the college basketball public betting splits, where the most intriguing dynamic on the board is unfolding in the moneyline market. The casual betting public is overwhelmingly backing Louisville, commanding a massive 77% of the betting tickets to win outright. However, when I shift my focus to the actual cash wagered the narrative completely flips.

A substantial 65% of the total handle is backing South Florida to pull off the upset. Because the ticket percentage for Louisville and the money percentage for South Florida both clear the definitive 60% threshold, this qualifies as a massive sharp money indicator. High-volume bettors and syndicates are taking a stand on the underdog.

Unlike the moneyline, the point spread market shows total alignment between the ticket count and the heavy cash. Currently, 60% of the betting tickets are taking the points with South Florida. More importantly, an overwhelming 73% of the total spread handle is also backing them. That puts my Louisville -4.5 bet in a deeply contrarian position. By laying the points, I am actively fading both the casual consensus and the sharp money, banking entirely on the massive strength of schedule disparity I outlined earlier.

As for the total splits, they’re far more balanced than the side markets. Bettors are showing a slight preference for a high-scoring shootout, with the Over drawing 51% of the tickets and a slightly higher 53% of the overall money.