March Madness First Four Predictions: Expert Picks, Spreads & Betting Trends for NCAA Tournament

Over the past ten years, the First Four in Dayton has grown to be a must-watch event, even if the full-fledged excitement of the 2025 NCAA Tournament doesn’t begin until Thursday with the First Round. As the final teams fight for a berth in the main bracket, these opening matchups set the tone for March Madness and provide high-stakes drama. The First Four never fails to provide thrilling moments, whether it’s conference champions vying for the right to face a No. 1 seed or the final at-large bids proving their place.

These early-round winners have the potential to make a significant impact, as history has demonstrated. At least one of these teams has advanced to the next round in 12 of the 13 tournaments since the First Four was first introduced. Some have gone even further—two programs, UCLA (2021) and VCU (2011), overcame the odds to reach the Final Four, while five teams have advanced to the Sweet 16.

Any one of these teams might be set for a deep tournament run as these high-stakes games finalize the field of 64. Four clubs will see an abrupt end to their season at the same time. For astute bettors searching for value picks, this focus creates incredibly thin betting lines and exciting opportunities.

Top Picks for Tuesday’s March Madness First Four Showdowns

Odds from SportsLine consensus | All times Eastern

(16) Alabama State vs. (16) Saint Francis

6:40 p.m. ET on TruTV | March Madness Live

Alabama State seized a prime opportunity in the SWAC Tournament following Southern’s unexpected exit, marking their fifth appearance in the NCAA Tournament. A crucial element in this matchup will be turnovers—an area where Alabama State excels while Saint Francis struggles.

The Hornets apply intense defensive pressure, ranking among the top 100 nationally in both turnover percentage and steals, which could create significant challenges for a Saint Francis team that ranks No. 321 and No. 355 in those same offensive categories. Anticipate Alabama State to capitalize on mistakes and convert defense into fast-break points, giving them the advantage.

Best Bet: Alabama State -3.5

(11) North Carolina vs. (11) San Diego State

9:10 p.m. ET on TruTV | March Madness Live

San Diego State has proven resilient in close contests, holding an impressive 8-2 record in games decided by six points or fewer. This highlights coach Brian Dutcher’s emphasis on defensive discipline, even as the offense has regressed compared to last year’s Sweet 16 team.

The Aztecs’ knack for slowing the pace and minimizing transition opportunities could challenge North Carolina, which thrives on fast breaks. If the Tar Heels find their rhythm from long range, they could outpace San Diego State’s scoring. However, against such a formidable defense, those open shots will be hard to come by.

Prepare for a tough, defensive showdown, with North Carolina managing just enough late-game execution to prevail in a lower-scoring contest.