🏀 South Florida vs. Louisville Prediction & Picks: March Madness Round 1 (March 19)

For 13 straight years, an 11 seed or higher has pulled off an upset within the first eight games of March Madness' Round 1.

Anyway, let's talk about the matchup between No. 6 Louisville and No. 11 South Florida on Thursday. Tipoff from KeyBank Center in Buffalo, N.Y., is set for 1:30 p.m. ET (TNT).

If it's not obvious, my South Florida vs. Louisville prediction likes the Bulls as a 5.5-point betting underdog. They will be one of the more popular upset picks for a reason, and I'm here to jump on the bandwagon as part of our March Madness predictions.

🏀 South Florida vs. Louisville picks & odds: March Madness Round 1

See all of our experts' college basketball picks based on the latest college basketball odds; picks rated on a 1-to-5 star confidence scale based on betting value.

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🏆 Who will win South Florida vs. Louisville?

See the latest March Madness odds for every team in the 2026 NCAA Tournament.

I'm predicting South Florida to pull off the upset with a 2-point win over Louisville in Thursday's Round 1 matchup. The Bulls enter this matchup on an 11-game win streak and have the physicality to power past the Cardinals on an off shooting night. As such, I'd be willing to back the +185 price tag on South Florida's moneyline value at DraftKings.

Score prediction: South Florida 83, Louisville 81

💰 South Florida vs. Louisville prediction & best bet

Follow all of our college basketball analysis and expert predictions for March Madness.

South Florida +5.5 (-110)

Louisville is a team that can go on a run, but it's also susceptible to an early upset because it lives and dies by the 3-ball. The Cardinals have the fourth-highest 3-point rate in the country, shooting 35.7% from distance. Louisville is 7-8 straight up this year when it shoots worse than 35% from 3-point range.

The Bulls are allowing opponents to shoot 33.9% on 3s this year. If Louisville's clip is closer to that (or worse), South Florida can easily hang in a battle of physical strength. The Bulls will generate extra possessions, as they rank seventh in the nation in offensive rebound rate at 38.2%.

It's easy to see why South Florida profiles as a popular upset pick. I'd expect this spread to drop more before tipoff, so I'm scooping up the +5.5 at FanDuel.

🔥 Best South Florida vs. Louisville player prop bet

Our March Madness betting trends break down which coaches have been the most profitable in the NCAA Tournament.

Wes Enis Over 2.5 3-pointers (-165)

March Madness is all about which players will deliver memorable moments and emerge as surprise characters in this tournament. I think South Florida guard Wes Enis is a candidate to be a March Madness hero.

This time last year, Enis was playing at the Division II level for Lincoln Memorial. Now, he's posted a 20-point performance seven times during South Florida's current 11-game win streak.

You can't leave this left-handed shooter open from deep, either. He's hit three or more triples in 19 of his 31 games, including seven of his previous 11 contests.

Enis' 3-point line is as high as 3.5 at FanDuel, so I'm taking the lone 2.5 at bet365 to back the South Florida guard on Thursday.

🚀 South Florida vs. Louisville same-game parlay

Because I don't have an opinion on the total, I've only put together a two-leg parlay for South Florida vs. Louisville. I'm on South Florida moneyline and the Over on Enis' 3-point prop. This parlay comes out to +290 at bet365, which is a shop worth exploring if you like an underdog this week. They are running a promo that offers an early payout for an underdog that goes up 10 in a game.

💡 How I'm betting South Florida vs. Louisville: March Madness strategy

As mentioned above, I think this game has upset written all over it. Louisville is too reliant on the 3-ball, while South Florida can create extra possessions. Plus, the Bulls have a potential March protagonist in the form of a former DII player.

This is a formula that has often led to upsets over the years. That's why I'm comfortable allocating 2.5 units into the South Florida side against Louisville. The spread is my favorite angle as long as it's flirting with two possessions, but the moneyline becomes more valuable if the line drops much further.

All aboard the Bulls' bandwagon in what should be the first upset of this year's tournament.

📊 Live South Florida vs. Louisville odds: March Madness Round 1

Louisville opened as a 6.5-point favorite, but the line has dropped to 5.5. The total has climbed from 164.5 to 165.5.

The early movement is an indication of where these markets might close ahead of tipoff. I expect South Florida's spread to be one of the more popular bets in Round 1.

📈 South Florida vs. Louisville betting trends

📺 How to watch South Florida vs. Louisville: March Madness Round 1

• Date: Thursday, March 19
• Tipoff: 1:30 p.m. ET
• Location: KeyBank Center (Buffalo, N.Y.)
• TV: TNT
• Streaming: HBO Max