Betting the East Region in 2026 NCAA Tournament: Predictions, Odds Upsets for March Madness

The East Region in the 2026 NCAA Tournament features the No. 1 overall seed (Duke), a team that has won two of the last three national titles (UConn) and the presumptive No. 1 overall pick in the 2026 NBA Draft (Darryn Peterson of Kansas).

So, bettors and college basketball fans are going to want to buckle up for this region’s games, as there should be a ton of high-level basketball, starting in the first round.

Duke is favored to win this region, but there are cases to be made for UConn, Michigan State, St. John’s and Kansas.

Here’s a look at all of the odds for this region, including the first-round matchup, and my picks to win the region and pull off an upset in Round 1.

Odds via FanDuel Sportsbook

East Region Opening Odds

No. 16 Siena vs. No. 1 Duke (-28.5)
No. 9 TCU vs. No. 8 Ohio State (-2.5)
No. 12 Northern Iowa vs. No. 5 St. John’s (-10.5)
No. 13 Cal Baptist vs. No. 4 Kansas (-14.5)
No. 11 South Florida vs. No. 6 Louisville (-5.5)
No. 14 North Dakota State vs. No. 3 Michigan State (-16.5)
No. 10 UCF vs. No. 7 UCLA (-5.5)
No. 15 Furman vs. No. 2 UConn (-20.5)

Odds to Win East Region

Duke: -130
UConn: +550
Michigan State: +750
Kansas: +1200
St. John’s: +1200
Louisville: +2000
UCLA: +2500
Ohio State: +4000
TCU: +10000
UCF: +17500
South Florida: +12500
Northern Iowa: +50000
Cal Baptist: +50000
North Dakota State: +50000
Furman: +50000
Siena: +50000

Each East Region Team’s Odds to Win March Madness

Duke: +380
UConn: +3500
Michigan State: +6000
Kansas: +8000
St. John’s: +8000
Louisville: +17500
UCLA: +20000
Ohio State: +40000
TCU: +100000
UCF: +100000
South Florida: +100000
Northern Iowa: +100000
Cal Baptist: +100000
North Dakota State: +100000
Furman: +100000
Siena: +100000

Predicting Who Will Win the East Region in 2026 NCAA Tournament

Duke (-130)

The Blue Devils earned the No. 1 overall seed in the NCAA Tournament, and Cameron Boozer has been the best college player this season.

I’m not going to let the injury to Caleb Foster sway me from picking the Blue Devils, who are fourth in KenPom’s adjusted offensive efficiency and second in adjusted defensive efficiency. In the last 23 NCAA Tournaments, 22 of the champions have finished in the top-25 in both adjusted offensive efficiency and adjusted defensive efficiency.

Duke fits this profile to a tee, and I think there are flaws for both St. John's and Kansas that should give the Blue Devils a path to the Elite 8. A matchup with UConn would be electric, but I trust Duke’s offense more than the Huskies at this point in the season.

East Region Upset Pick and Prediction

South Florida (+185) vs. Louisville

A lot of this game rests on the health of Louisville star guard Mikel Brown Jr., who is day-to-day ahead of the NCAA Tournament after missing the ACC Tournament. That makes the South Florida Bulls an interesting upset pick in the first round of this tournament.

South Florida needed to win the AAC to get into the field, but the Bulls have an impressive defensive resume, ranking 40th in adjusted defensive efficiency, per KenPom. The Bulls are also:

47th in opponent effective field goal percentage
56th in opponent turnover rate
24th in opponent 2-point percentage.

South Florida loves to push the pace, ranking 15th in KenPom’s adjusted tempo metric, and I love targeting teams that play unique styles in these upset spots.

Louisville has a pretty strong profile, but the ACC wasn’t super deep this season, as shown by just two teams (Duke and Virginia) receiving better than a No. 6 seed in the tournament. South Florida would be a must-bet for me if Brown ends up missing the first round.