March Madness Round of 64 Predictions, Picks & Odds for SIUE vs Houston

• 16-seed SIU Edwardsville is a massive 29-point underdog vs 1-seed Houston
• There are reasons to believe SIUE can cover this huge March Madness spread
• See our SIUE vs Houston prediction and betting pick below

The 2025 NCAA Tournament tips off Thursday afternoon afternoon with what appears to be a colossal mismatch between the 1-seed Houston Cougars (30-4) and 16-seed SIU Edwardsville Cougars (22-11).

Houston is laying a whopping 29 points on the March Madness odds board in this 2:00 p.m. ET tip at INTRUST Bank Arena in Wichita, KS.

But are the Cougars being overvalued by oddsmakers?

SIUE vs Houston Prediction (March Madness Round of 64)

On paper, this looks like a blowout waiting to happen. Houston ranks 3rd overall in KenPom, with the nation’s 2nd rated defense and a top-10 offense. They demolished opponents en route to the Big 12 regular season and tournament titles. Meanwhile, SIU needed a surprising run in the Ohio Valley Conference tourney as a 2-seed just to reach March Madness.

But look a little deeper, and you’ll find reasons SIU might hang around in this Round of 64 matchup. Most importantly, Houston plays at a snail’s pace – ranking 360th out of 363 teams in adjusted tempo. Fewer possessions means fewer chances for favorites to run up a huge margin like 29 points.

Historically, even dominant No. 1 seeds have struggled to consistently cover spreads this large in past NCAA tournaments. Their main goal? Win and move on. Style points don’t matter. If Houston builds a comfortable lead early, don’t be surprised if they rest their starters to avoid injuries or fatigue.

The Cougars also haven’t been great against the spread (ATS) lately—just 2-4 in their last six games and 16-14-1 on the season. They’ve failed to cover much smaller spreads than this, which makes the 29-point line feel more like public perception than an accurate reflection of the matchup. My true line would be closer to 25 points for this matchup if we’re aiming for a 50/50 betting scenario.

On the SIU Edwardsville side, their defense is better than your typical 16-seed. They rank 51st nationally in scoring defense (allowing just 66.1 PPG) and 32nd in opponent shooting percentage (40.2%). If they can turn this into a gritty, physical game, the backdoor cover becomes a real possibility.

SIUU has also locked down the perimeter all season – bad news for a Houston team that relies heavily on the three-ball (39.8% from deep as a team). If Houston goes cold from downtown, covering this spread becomes a tall task. SIUE also plays a more modern style, shooting over 36% of their attempts from downtown, which gives them a puncher’s chance of scoring in spurts.

Lastly, SIUE has a legit star in guard Ray’Sean Taylor, who averages 19.3 points per game. He’s the type of dynamic scoring threat that could give Houston some problems and is capable of keeping his team within striking distance.

SIU Edwardsville vs Houston Pick

• SIU +29 (-110) at Caesars

CAESARS SPORTSBOOK

Bet $1 & Double Your Winnings On Your First 10 Bets!

LOCK IN PROMO

CODE: SBD2DYW

CODE: SBD2DYW

SIGNUP PROMO

DOUBLE YOUR
WINNINGS

ON YOUR FIRST 10 BETS!

CLAIM OFFER

To be clear, I’m not calling for a historic 16-over-1 upset. But SIUE has all the ingredients of a pesky underdog. Their slow tempo, solid defense, three-point shooting potential, and go-to scorer make them a real threat to cover this huge spread. Houston is focused on advancing, not running up the score, which adds even more value to SIUE in this spot.

College basketball public betting trends show 62% of spread handle and a massive 98% of the moneyline money backing Houston. That feels like an overreaction to the No. 1 vs. No. 16 narrative.

However, SIUE is built to keep this respectable with its slow, defensive-minded approach and potential for a hot 3-point shooting night. As long as Houston doesn’t shoot the lights out, this game should stay with the number and go under the total.

SIUE vs Houston Odds & Betting Lines

This is the largest spread for any March Madness Round of 64 games, with oddsmakers implying there is a 90.9% implied probability Houston wins and advances. Houston is -1000 on the moneyline and -29 against the number.

The best line for SIUE +29 is at Caesars Sportsbook at -110 odds. The Cougars are +3300 on the moneyline if you want to dream really big, while the game total is set at 126.5 points.

Odds as of March 19th at Caesars. Check out the best March Madness betting apps for Round of 64.