🏀 South Florida vs. Louisville Prediction & Parlay Today: March Madness Picks & Odds

South Florida opens its 2026 March Madness run against Louisville, aiming to continue a trend where an 11-seed or lower has pulled off at least one upset in the first eight games of Round 1 in each of the past 13 tournaments. My South Florida vs. Louisville prediction for this matchup backs the Bulls as a 5.5-point underdog against the No. 6 Cardinals, with tipoff set for 1:30 p.m. ET at KeyBank Center on TNT.

South Florida is one of the more popular upset picks this week as part of our March Madness predictions, and I'm here to jump on the bandwagon.

🏀 South Florida vs. Louisville picks & odds today

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.

Total wagered: 2.5 units | Max profit: 2.35 units

🏆 Who will win South Florida vs. Louisville?

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

I’m calling for South Florida to pull off the upset, edging Louisville by two points in Thursday's Round 1 matchup. The Bulls come in riding an 11-game winning streak and have the physical edge to push past the Cardinals if Louisville struggles to shoot. At +185, there’s enough value on South Florida’s moneyline to make it worth a play.

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 competing at the Division II level with Lincoln Memorial. Now, he’s erupted for 20 points in seven games during South Florida’s current 11-game winning 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

Since I don’t have a strong lean on the total, I’ve built a two-leg parlay for South Florida vs. Louisville. I’m backing South Florida on the moneyline along with the Over on Enis' 3-point prop. This combo pays out at +290 on bet365, making it a solid option if you’re targeting an underdog this week - especially with their promo offering an early payout if your underdog jumps out to a 10-point lead.

💡 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 today

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: Max

🆚 March Madness first-round matchups & previews

Here is the first-round March Madness schedule, and our betting preview:

🏀 March Madness bracket previews: East | Midwest | West | South

Bracket picks & odds analysis