March Madness Second Round Odds for All 16 Games

• The March Madness second-round matchups have started to materialize and odds are out for the first few matchups
• Auburn is a sizable favorite over Creighton in the first second-round game to be posted
• See the March Madness second round odds (spread, moneyline, total) for all games as they become available

The first real day of the 2025 NCAA Tournament is more than half over and odds are starting to come out for second-round games, which will take place on Saturday and Sunday. The table below lists the opening odds for all round-of-32 matchups (spread, moneyline, and game total). It will be continually updated until all 16 second-round games are on the board.

Second Round March Madness Odds

The first game on the board is #8 Creighton vs #1 Auburn in the South Regional. The second round-of-32 matchup to be set was potential Cinderella #12 McNeese against #4 Purdue in the Midwest.

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Odds as of March 21 at DraftKings. Download the best March Madness betting apps before the second round begins.

Though neither has set foot on the court yet, East #1 Duke and West #1 Florida remain the top-two favorites in the March Madness championship odds at +320 and +380, respectively.

Auburn Opens as Big Favorite Over Creighton

The Creighton Bluejays were impressive in an 89-75 throttling of Louisville in what amounted to a road game in Lexington, Kentucky. Jamiyah Neal was sublime with 29 points, 12 rebounds, and six assists on a career-best night for the senior guard. Creighton’s size and perimeter shooting proved the difference. The Bluejays finished +4 on the glass with five blocks (all from seven-foot center Ryan Kalkbrenner) and connected at a 46% clip from beyond the arc.

Creighton was a +3000 longshot in the odds to reach the Final Four before beating Louisville as 3.5-point underdogs. The Bluejays shortened to +1500 after the lopsided victory.

Auburn needed almost a full half to get going against #16 Alabama State, a team they were favored to beat by 32 points. The lead was just three points late in the first half but the Tigers would stretch it to ten before the break and win the second half by the same margin en route to an 83-63 win. Johni Broome had another double-double with 14 points and 11 rebounds.

Auburn moved from roughly even-money to -130 in the Final Four odds. Creighton is perceived to be an easier opponent than Louisville would have been largely due to these games taking place in Kentucky.

Purdue Favored Over McNeese But Line Is Already Moving

The #4 Boilermakers opened as 7.5-point favorites over #12 McNeese but before I could even write a sentence the line had moved to 6.5. The Purdue moneyline went from -325 to -285. McNeese opened as a +260 underdog on the moneyline and is now +230.

McNeese wound up only beating #5 Clemson by two points (69-67) but the win didn’t feel in doubt after about the 15-minute mark. The Cowboys led by 18 at halftime and the only lead grew early in the second half. Clemson didn’t make it a single-possession game until the last second of the game, though they did make a spirited comeback attempt.

Purdue beat #13 High Point comfortably, 75-63, leading by ten at halftime and never getting seriously threatened in the final 20 minutes. Trey Kauffman-Renn’s size was just too much for the Panthers; the Purdue forward and leading scorer finished with a game-high 21 points and eight rebounds while shooting 62.5% from the floor.

Houston Favored Over Zags in Midwest

On paper, the best game of the second round – which I can say even before seeing the other 12 matchups – will see the #1 Houston Cougars face the #8 Gonzaga Bulldogs in the Midwest Region. Gonzaga has made nine straight Sweet 16s but has opened as a 5.5-point underdog to the Cougars.

Houston has won 14 straight games and only dropped four all season (one since the start of December). In their last four victories, which includes the Big 12 Tournament and first-round rout of SIU Edwardsville, Houston as a 21.3-point average margin of victory.

Gonzaga comes in hot, as well, though. They’ve won four straight, including a 58-51 win over Saint Mary’s in the WCC Tournament final and today’s 89-68 obliteration of the #9 Georgia Bulldogs.