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Louisville Cardinals vs Michigan State Spartans Picks

KeyBank Center

<p>I hope you didn&#8217;t blink yesterday, because you may have missed some incredible basketball, and before we know it, the tournament is going to be halfway over! There are only 63 total games in this tournament (excluding the first four), so after Thursday and Friday, we have a finite amount of games left in the season. Thankfully, we are in for a thriller early on Saturday as Tom Izzo and Pat Kelsey lead their teams into Buffalo for this Round of 32 matchup. Can the Louisville Cardinals or Michigan State Spartans come out on top? Let&#8217;s get into our favorite picks and find out.</p>
<p><a href="/ncaab/march-madness/">Check out our March Madness Betting Guide</a> to get in on all the action this month!</p>
<h3><a href="https://affiliates.bettingnews.com/register/luckyrebel-articles/" target="_blank" rel="noopener">Best Bet: Michigan State -4.5 (-110) Lucky Rebel Sportsbook</a></h3>
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<p><a href="/author/nate/">Go check out what else I&#8217;ve got on</a> my daily card, and view the latest odds at the <a href="/best-online-sportsbooks/">best online sportsbooks.</a></p>
<h2><a href="/ncaab/matchup/2026-03-21-louisville_cardinals-michigan_state_spartans-n-1/">#6 Louisville Cardinals vs. #3 Michigan State Spartans NCAA Basketball Insights</a></h2>
<div id="attachment_88614" style="width: 1033px" class="wp-caption alignnone"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-88614" class="size-full wp-image-88614" src="https://wp.bettingnews.com/wp-content/uploads/2025/11/Khani-rooths-louisville-basketball-picks.jpg" alt="Can Louisville shoot as well as they did in the Round of 64 against the Spartans? Michigan State Louisville Picks" width="1023" height="576" srcset="https://wp.bettingnews.com/wp-content/uploads/2025/11/Khani-rooths-louisville-basketball-picks.jpg 1023w, https://wp.bettingnews.com/wp-content/uploads/2025/11/Khani-rooths-louisville-basketball-picks-300x169.jpg 300w" sizes="auto, (max-width: 1023px) 100vw, 1023px" /><p id="caption-attachment-88614" class="wp-caption-text">Can Louisville shoot as well as they did in the Round of 64 against the Spartans?</p></div>
<p>I was very heavy on South Florida to take down the Cardinals in the Round of 64, and they came extremely close. On the other sideline, Michigan State handled business against North Dakota State. Ultimately, I think the Spartans are the far better team in this spot, and the books think so as well, as they are 4.5 point favorites over the Cardinals.</p>
<p>But Louisville shot the lights out of the gym yesterday against the Bulls, who can hold their own defensively. Will Tom Izzo&#8217;s defensive minded team be able to slow them down and limit their chances? I certainly think so.</p>
<h3>Matchup Information &#8211; Louisville vs. Michigan State &#8211; March 21</h3>
<ul>
<li>Venue &amp; Location: KeyBank Center (Buffalo, NY)</li>
<li>Date: Saturday, March 21, 2026</li>
<li>Kick Off: 2:45 p.m. Eastern</li>
<li>Broadcast: CBS</li>
</ul>
<h3>Louisville vs. Michigan State Betting Odds</h3>
<p><em><a href="https://affiliates.bettingnews.com/register/luckyrebel-articles/" target="_blank" rel="noopener">Odds are courtesy of Lucky Rebel</a>, one of our favorite online sportsbooks, as of March 20, 2026 at 1:30 p.m. eastern. Sign up today with and get a $1,250 deposit bonus, as well as 50 slot spins immediately. Lucky Rebel Sportsbook offers a wide variety of unique markets across nearly every sport imaginable.</em></p>
<h4>Spread</h4>
<ul>
<li>Louisville +4.5 (-110)</li>
<li>Michigan State -4.5 (-110)</li>
</ul>
<h4>Moneyline</h4>
<ul>
<li>Louisville +165</li>
<li>Michigan State -190</li>
</ul>
<h4>Total</h4>
<ul>
<li>Over 151 (-110)</li>
<li>Under 151 (-110)</li>
</ul>
<h2><a href="/ncaab/matchup/2026-03-21-louisville_cardinals-michigan_state_spartans-n-1/">#6 Louisville vs. #3 Michigan State NCAA Basketball Picks and Predictions</a></h2>
<div id="attachment_98492" style="width: 1210px" class="wp-caption alignnone"><img loading="lazy" decoding="async" aria-describedby="caption-attachment-98492" class="wp-image-98492 size-full" src="https://wp.bettingnews.com/wp-content/uploads/2026/02/jeremy-fears-michigan-state-basketball.jpg" alt="Jeremy Fears and the Spartans will need to guard the perimeter against the Louisville Cardinals - Michigan State Louisville Picks" width="1200" height="676" srcset="https://wp.bettingnews.com/wp-content/uploads/2026/02/jeremy-fears-michigan-state-basketball.jpg 1200w, https://wp.bettingnews.com/wp-content/uploads/2026/02/jeremy-fears-michigan-state-basketball-300x169.jpg 300w, https://wp.bettingnews.com/wp-content/uploads/2026/02/jeremy-fears-michigan-state-basketball-1024x577.jpg 1024w" sizes="auto, (max-width: 1200px) 100vw, 1200px" /><p id="caption-attachment-98492" class="wp-caption-text">Jeremy Fears and the Spartans will need to guard the perimeter against the Louisville Cardinals</p></div>
<h3>Louisville vs. Michigan State Prediction: Michigan State Wins and Covers, Over 151</h3>
<h3><a href="https://affiliates.bettingnews.com/register/luckyrebel-articles/" target="_blank" rel="noopener">Best Bet: Michigan State -4.5 (-110) Lucky Rebel Sportsbook</a></h3>
<div aria-label="Page 1" data-page-number="1">
<p class="p1">Let&#8217;s look at what Louisville did yesterday. They shot 54% from the field and 52% from deep, while the Bulls were just 39% overall and 15% from downtown. Plus, the Bulls excelled in the turnover battle, forcing 22 from the Cardinals while only giving up nine. The Cardinals only won that game because they made 13 of their 25 threes. That&#8217;s it. Do we really expect that to happen again? Short answer, no.</p>
<p>Michigan State is a VERY good defensive team, and even though they don&#8217;t force turnovers, they rank top 90 in opponent 3P%. I am betting that there is no way Louisville shoots that well again, so we&#8217;re expecting some regression. While the Spartans&#8217; offense doesn&#8217;t wow me night in and night out, they can hold their own against a front court that isn&#8217;t too daunting. Plus, Michigan State is top 10 in rebounding on both sides of the ball (leading the country in defensive boards), while the Cardinals are outside the top 90 in grabbing boards.</p>
<p>If it comes down to free throws, Sparty certainly has the advantage, and I&#8217;ll be backing them to win this game with their defensive presence.</p>
</div>
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<h2>Bet on March Madness at Lucky Rebel and BetOnline</h2>
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<h2>Check Out the Other March Madness Content from Betting News</h2>
<p>For college basketball bettors, March Madness is the most wonderful time of the year. And at Betting News, we have you covered for this festively fun season with expert picks throughout the tournament from <a href="/author/nate/">Nate Hornung</a> and <a href="/author/eg/">Eddie Griffin</a>, <a href="/ncaab/picks/">consensus picks for every March Madness game</a> from the First Four to the Final Four, a rundown of the best March Madness betting sites, and more.</p>
<p>Also, through our streams and social media channels, you can get even more insight from Nate and other members of the Betting News team, as well as offer your own thoughts and tips for the tournament.</p>
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<p>To find out when you can catch Nate chatting about the climax of the college basketball season and learn about our current lineup of sports betting streams, check out the <a href="/sports-betting-shows/">Betting News Network schedule</a>.</p>
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