Louisville vs. Michigan State prediction: Why Michigan State is favored to win men's March Madness Second Round matchup [3/21/2026]

Michigan State will square off with Louisville in March Madness Second Round action at KeyBank Center on Saturday, beginning at 2:45 PM ET.

For this Second Round clash, Michigan State—a Tom Izzo defense that thrives in transition— take on Louisville, a guard-heavy roster living up to its Guard U. identity.

Based on updated simulations, Dimers' proven college basketball model predicts Michigan State as the most likely winner of the Louisville vs. Michigan State game.

This article offers a closer look at Saturday's matchup, including an expanded look at the predicted score, best bets and picks.

Louisville vs. Michigan State prediction: Who will win and advance to the Sweet Sixteen?

Using powerful machine learning and data, we have simulated the outcome of Saturday's NCAAM Tournament game between Louisville and Michigan State 10,000 times as part of our men's college basketball predictions coverage.

Our famous predictive model currently gives Michigan State a 75% chance of beating Louisville. Our predicted final score has Michigan State winning 79-71.

According to our model, Michigan State (-5.5) has a 58% chance of covering the spread, while the 151.5-point over/under has a 52% chance of staying under.

Louisville vs. Michigan State odds

We have sourced the best men's college basketball odds in America for this game, which are listed here:

Bet Type	Louisville	Michigan State
Spread	+5.5 (-105)	-5.5 (-108)
Moneyline	+215	-235
Total	o151.5 (-110)	u151.5 (-105)

All odds are correct at the time of publication and are subject to change.

Louisville vs. Michigan State picks and best bet

After matching our predictions against the best available odds, we can reveal our picks for each of the major markets. Plus, find our best bet for the game below:

Bet Type	Pick	Bet Now
Spread	Michigan State -5.5	-108
Moneyline	Michigan State	-235
Total	Under 151.5	-105

According to our best men's college basketball bets, the top play to make on this game is Michigan State -5.5 at the spread.

These picks are based on our probabilities matched against the implied probabilities from the sportsbook odds.

Louisville vs. Michigan State game-day updates and essential details

Saturday's men's college basketball matchup between Michigan State and Louisville at KeyBank Center is scheduled to begin at 2:45 PM ET.

• Who: Louisville vs. Michigan State
• Date: Saturday, March 21, 2026
• Time: 2:45 PM ET/11:45AM PT
• Venue: KeyBank Center
• March Madness stage: Second Round

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Conclusion

We predict Michigan State, with a 75% win probability, will likely beat Louisville this men's March Madness Second Round matchup.

AI and automation have enhanced this article to quickly deliver accurate Louisville vs. Michigan State insights, with human oversight ensuring high editorial quality. Our predictions are based on the latest data to help you make informed decisions. For additional resources and advice on responsible gambling, please call 1-800-GAMBLER.

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