🏀 Siena vs. Duke Prediction & Picks: March Madness First Round (March 19)

The East Region's No. 1 seed, Duke, has the shortest March Madness national championship odds, and its quest for a title begins against No. 16 seed Siena. 

My Siena vs. Duke prediction backs the Blue Devils with the gap seemingly widening between mid-majors and the sport's blue bloods in the NIL era. I also add a Cayden Boozer player prop as he is coming off back-to-back season-highs in points in the last two ACC Tournament wins.

The game tips from Bon Secours Wellness Arena in Greenville, S.C., at 2:50 p.m. ET on Thursday, airing on CBS. The Blue Devils are a 29.5-point betting favorite, as we make all of our March Madness predictions. 

🏀 Siena vs. Duke picks & odds: March Madness First Round

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.

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🏆 Who will win Siena vs. Duke?

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

Duke has the best Final Four and national championship odds of all the No. 1 seeds. As the overall No. 1 seed playing against a team that was a No. 3 seed in its conference tournament, the Blue Devils are in no danger of becoming the third No. 1 seed to lose to a No. 16, and should win by 30-plus.

Score prediction: Duke 84, Siena 51

💰 Siena vs. Duke prediction & best bet

Duke -29.5 (Odds)

Duke received bad news when Caleb Foster and Patrick Ngongba were ruled out for the ACC Tournament. But its strength lied in Cameron Boozer and the hot shooting of Isaiah Evans of late anyway, and the lack of depth shouldn’t hurt the Blue Devils’ chances of covering against Siena.

This mismatch is one of the biggest reasons there is a plus-42.51 AdjEM gap between the No. 1 and No. 16 seeds, the second-highest all-time. Siena’s undoing will be a defensive turnover rate that lowered to 15.8% in MAAC play (11th-worst), meaning Duke will have plenty of clean possessions.

🔥 Best Siena vs. Duke player prop bet

Cayden Boozer Over 10.5 points (+102)

Duke head coach Jon Scheyer likely knows the importance of Boozer’s play going forward, as his emergence in the absence of Caleb Foster could be the difference between the Blue Devils winning or not winning a national championship. I expect Scheyer to put Boozer in a position to continue to build confidence after a strong ending to the ACC Tournament.

Florida State had success in the quarterfinal of the conference tournament in slacking off Boozer in order to give his brother, Cameron, more defensive attention. Cayden must’ve taken that as a slight, scoring 16 points apiece in the next two games, while playing season-highs in minutes (37 and 40, respectively).

Siena limited opponents to a MAAC best 36.4% scoring from 3-point range. But 3-point shooting isn’t Boozer’s specialty anyway, and he should get the bulk of these points in transition.

🚀 Siena vs. Duke same-game parlay

If Duke is going to cover this big spread, it will likely need more from the supporting cast outside of Cameron Boozer and Isaiah Evans. That is why I'm backing the Over on Cayden Boozer's points, but still expect a dominant defensive effort to help keep the game under the projected total.

💵 My betting record for college basketball

All college basketball picks, including SGPs, have been tracked since March 13.

💡 How I'm betting Siena vs. Duke: March Madness strategy

Follow all of our college basketball analysis and expert predictions for March Madness.

I'm much more confident in Duke covering than I am about the total, as I expect the Blue Devils to play most of their starters meaningful minutes to try and develop chemistry as a result of the newly developed injuries. But when the game gets out of hand late, I do not want to have to be sweating points on the total in case there is a less-focused defensive effort, which is why the Under is only a half-unit play.

📊 Live Siena vs. Duke odds: March Madness First Round

The only line movement thus far from a point spread perspective was at bet365, who quickly aligned with the rest of the market at -29.5 after opening at 29. Given that Duke is such a public team with casual bettors expecting dominance out of No. 1 seeds, I wouldn't be surprised to see this line reach -30 or higher before tip.

📈 Siena vs. Duke betting trends

📺 How to watch Siena vs. Duke: March Madness First Round

• Date: Thursday, March 19
• Tipoff: 2:50 p.m. ET
• Location: Bon Secours Wellness Arena (Greenville, S.C.)
• TV: CBS
• Streaming: Paramount+