2025 NCAA Tournament : Sweet 16 Matchups, Predictions & Betting Picks

The first tickets to the Sweet 16 will be secured as the second round of the 2025 NCAA Tournament kicks off on Saturday. While the number of matchups has decreased with the field narrowing from 64 to 32, the intensity has only increased. Saturday’s second-round action presents a chance to evaluate the three double-digit seeds that advanced from the first round on Thursday through surprising victories.

A major storyline will be whether McNeese or Drake can continue their Cinderella run as they face power-conference opponents determined to end their dream season. Additionally, we will witness a battle between two Naismith Memorial Hall of Fame coaches, as Rick Pitino and St. John’s take on John Calipari and Arkansas. The two No. 1 seeds in action, Auburn and Houston, will also be tested by formidable opponents—Creighton and Gonzaga, respectively—who delivered dominant first-round performances.

After thoroughly analyzing the eight-game slate, we’ve identified key betting picks, starting with another strong showing from Will Wade and the McNeese Cowboys.

Odds via SportsLine consensus | All times Eastern

Best Bets for Saturday’s Second-Round Games

(2) St. John’s vs. (10) Arkansas

2:40 p.m. on CBS | March Madness Live: Few coaches in America are as trusted as Rick Pitino when it comes to quick scouting and game planning on a short turnaround. The Johnnies had a slow start against Omaha but found their shooting rhythm in the second half. If Arkansas allows open looks, St. John’s can capitalize in ways Kansas couldn’t. St. John’s is 11-3-1 against the spread in road or neutral-site games this season due to their strong defense and Pitino’s ability to prepare his team for tough environments. Pick: St. John’s -7.5

(3) Texas Tech vs. (11) Drake

6:10 p.m. on TNT | March Madness Live: This is a surprisingly low line for two teams that are both highly efficient on offense. Drake ranks No. 362 out of 364 Division I teams in transition offense, but their excellent offensive rebounding allows them to generate second-chance points in the half-court. As an underdog, Drake will need to stay aggressive and avoid slowing the game down. Texas Tech, on the other hand, boasts one of the most efficient offenses in the country and has strong spacing and three-point shooting. Given the scoring capabilities on both sides, a total in the low 130s seems more appropriate. Pick: Over 127.5

(3) Wisconsin vs. (6) BYU

7:45 p.m. on CBS | March Madness Live: BYU has been impressive in the latter half of the season and successfully avoided an early exit against VCU. The Cougars’ depth is a key strength, with eight players averaging double-digit minutes and multiple scoring threats capable of leading the team. Their versatility makes them a difficult opponent for Wisconsin, which has struggled defensively against elite competition. Pick: BYU +1

(1) Houston vs. (8) Gonzaga

8:40 p.m. on TNT | March Madness Live: There may be an overreaction to Gonzaga’s dominant first-round win over Georgia. While the Bulldogs looked fantastic, they faced a team with little recent NCAA Tournament experience. Houston, on the other hand, is on a completely different level and showcased elite defense in their opening-round win over SIU-Edwardsville. The Cougars’ defensive pressure will disrupt Gonzaga’s guards, preventing their high-powered offense from getting into a rhythm. Pick: Houston -5.5

(4) Purdue vs. (12) McNeese

12:10 p.m. on CBS | March Madness Live: Will Wade’s McNeese Cowboys exceeded expectations with their first-round upset of Clemson. McNeese has been strong against the spread this season, covering against Alabama, Clemson, and Mississippi State in road or neutral-site games. Purdue, meanwhile, has struggled with defensive consistency and relies heavily on Braden Smith to run the offense. If McNeese’s defensive pressure disrupts Smith, they can keep the game close. Pick: McNeese +6

Get every pick, prediction, and upset alert for March Madness! Visit SportsLine now to see which teams will make and break your bracket, and find out who will cut down the nets—all from the model that has outperformed 91% of CBS Sports bracket players in four of the last six tournaments.