Computer Picks for March Madness Games Today – A.I. Best Bets on March 21)

• Our A.I. model has made its March Madness picks for Saturday, March 21
• See the top computer pick for all 8 NCAA Tournament second-round games today

The first round of the NCAA Tournament produced multiple upsets — but all four No. 1 seeds survived.

Will the No. 1 seeds all reach the Sweet 16 for the third consecutive year? Stay tuned.

Today, we’ll get half of that answer as No. 1 seeds Michigan (Midwest) and Duke (East) highlight the 8-game slate in the second round of the NCAA Tournament. Michigan starts the day with a 12:10 pm, ET tip-off against upset-minded Saint Louis.

I asked Sportradar’s proprietary A.I. model to generate its best spread bet for all 8 games. The table summarizes the picks, which I line-shopped across all available sportsbooks and prediction sites.

A.I. March Madness Picks & Computer Predictions

#9 Saint Louis vs #1 Michigan Pick & Analysis (Midwest Region)

The Pick: Saint Louis +12.5 ($0.50 per contract at Kalshi, or +100 odds)

The market is severely overvaluing the projected pace in this clash between Saint Louis and Michigan. Oddsmakers opened the total at a staggering 161.5, heavily weighting Michigan’s frontcourt efficiency spearheaded by big men Aday Mara and Morez Johnson Jr. However, the Billikens orchestrate a methodical, defensively sound scheme that deliberately slows the game down. Saint Louis guards Dion Brown and Amari McCottry are highly effective at attacking drop coverage, allowing the Billikens to utilize the entire 30-second shot clock while generating efficient mid-range looks. By artificially deflating the total number of possessions, Saint Louis mathematically restricts Michigan’s ability to stretch the lead beyond double digits. Take the points with the underdog.

#6 Louisville vs #3 Michigan State Pick & Analysis (East Region)

The Pick: Michigan State -4.5 (-110 at FanDuel)

Louisville is reeling from the loss of star guard Mikel Brown Jr., whose back injury completely fractures their offensive initiation. Without their primary ball-handler, who averaged 4.7 assists per game during the regular season, the Cardinals coughed up an alarming 23 turnovers in their opening-round matchup. Michigan State, spearheaded by the elite perimeter defense of Jeremy Fears Jr., will heavily pressure Louisville’s makeshift backcourt. The Spartans will consistently punish those live-ball turnovers. Despite the absence of Brown, Louisville guard Ryan Conwell (18.7 PPG) pushes a frantic pace that prevents prolonged scoring droughts. Michigan State will comfortably cover the -4.5 spread via transition efficiency.

#9 TCU vs #1 Duke Pick & Analysis (East Region)

The Pick: TCU +11.5 (-110 at BetMGM)

Duke faces a massive situational disadvantage inside the paint today, presenting a distinct betting edge for the underdog. TCU is perfectly constructed to exploit this gap, leaning on their bruising frontcourt tandem of Micah Robinson and David Punch. By controlling the glass and generating second-chance points, the Horned Frogs can dictate a grinding, half-court tempo that inherently limits total possessions. Back the Horned Frogs to dominate the interior and keep the margin tight.

#10 Texas A&M vs #2 Houston Pick & Analysis (South Region)

The Pick: Houston -10.5 (-110 at Caesars)

Houston demonstrated their suffocating defensive prowess in the opening round, holding Idaho to just 47 points. Texas A&M prefers a gritty, rebounding-focused style, but the Cougars are uniquely equipped to neutralize the Aggies on the glass. Expect Houston’s relentless pressure to wear down Texas A&M over 40 minutes, leading to a comfortable double-digit victory and a cover for the favorites.

#11 Texas vs #3 Gonzaga Pick & Analysis (West Region)

The Pick: Texas +6.5 (-110 at Bet365)

According to college basketball public betting splits, massive sharp money handle is flowing toward the Longhorns despite the public favoring Gonzaga. Texas looked dynamic in their opening-round upset over BYU, and their athletic backcourt can challenge the Bulldogs’ perimeter defense. Back the Longhorns to keep this game highly competitive or pull off the outright upset against a Gonzaga squad that looked vulnerable at times against Kennesaw State.

#11 VCU vs #3 Illinois Pick & Analysis (South Region)

The Pick: VCU +11.5 (-110 at Bet365)

Offensive variance heavily favors VCU in this matchup against Illinois, specifically due to the Rams’ high-volume perimeter shooting. VCU operates through the isolation scoring of guard Terrence Hill Jr., who drastically stretches opposing defenses and forces opposing big men to step out of the paint. While Illinois boasts a massive interior advantage with forward David Mirkovic, their defensive rotations on the perimeter leave them vulnerable from beyond the arc. Because VCU actively hunts transition threes and Illinois reliably pounds the offensive glass for put-backs, both teams will execute high-percentage scoring models without chewing down the shot clock. Expect a fast-paced shootout, giving the Rams more than enough offensive firepower to stay inside the 11.5-point number.

#5 Vanderbilt vs #4 Nebraska Pick & Analysis (South Region)

The Pick: Nebraska +2.0 (-105 at Bet365)

Nebraska is riding the momentum of their first-ever NCAA Tournament win, fueled by a red-hot shooting performance from Pryce Sandfort. While Vanderbilt looked composed in their return to the tournament, the Cornhuskers’ perimeter spacing and motion offense present a challenging matchup for the Commodores. Take the points with Nebraska in what projects to be a tightly contested, back-and-forth affair.

#12 High Point vs #4 Arkansas Pick & Analysis (West Region)

The Pick: Arkansas -11.5 (-110 at Bet365)

High Point pulled off an incredible stunner against Wisconsin, but its Cinderella magic will face a severe reality check against SEC Tournament champion Arkansas. The Razorbacks boast overwhelming size, athleticism, and depth that the Panthers will struggle to match for a full game. Arkansas poured in 97 points in its opener and will aggressively use their transition game to pull away in the second half, covering the large spread.

All odds are subject to change

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