March Madness odds, lines, point spreads: The best bets and parlays for picking Sweet 16 games

The first weekend of the 2026 NCAA Tournament is in the rearview mirror. 

After upsets and buzzer beaters, 16 teams have emerged from the madness and have advanced to the next weekend of the tournament. Looking at the Sweet Sixteen matchups, all of the better seeds are favored to advance to the Elite Eights. With fans complaining that the Cinderella teams are dead, teams like No. 11 Texas and No. 9 Iowa have a chance to keep their championship hopes alive with big upset wins in the second weekend. 

The highest point spread of the weekend sees No. 1 Michigan as a 10.5-point favorite over No. 4 Alabama. The smallest spread has No. 4 Nebraska as the slim 1.5-point favorites over No. 9 Iowa. The point totals range from 133.5 points for Nebraska and Iowa all the way to 174.5 for Michigan and Alabama in what projects to be another wild weekend of men's college basketball. 

Here are the best bets, predictions and more for the Sweet Sixteen of the 2026 NCAA Tournament. 

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March Madness odds for Sweet Sixteen

Odds courtesy of DraftKings Sportsbook.

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March Madness best bets for Sweet Sixteen

No. 5 St. John's (+6.5) vs. No. 1 Duke 

Duke entered the 2026 NCAA Tournament as the overall No. 1 seed in the tournament after losing just two games during the regular season. The Blue Devils had an opening-round scare against No. 16 Siena, but escaped with a six-point win. Duke was on upset watch again in the second round, getting off to an uncharacteristically slow start against TCU. Luckily for the Blue Devils, they bounced back, and in combination with the Horned Frogs going ice cold from the field, it looks after the fact like it was a blowout victory.

At some point, Duke's recent trend of starting slowly in games is going to catch up to them, and they won't be able to out-talent their way to a full comeback against teams that don't have quite the same talent gap. 

The Blue Devils will match up with the St. John's Red Storm in the Sweet 16. St. John's beat Northern Iowa by 26 in the first round and escaped against No. 4 Kansas with a two-point win in the Round of 32. It will have to take the Red Storm playing one of its most well-rounded games of the season, but head coach Rick Pitino has already talked about how much this game means to him, and he wants revenge for Duke and Christian Laettner ending his tournament run with Kentucky in 1992. 

There is a good chance that St. John's wins this game outright, but at the very least, the Red Storm should keep it close. The only worry with this kind of bet is late-game free throws that could make or break a spread, but St. John's should cover in a tight game. 

No. 3 Illinois vs. No. 2 Houston: Over 139.5 points

Obviously, not every matchup is going to be a scoring extravaganza, but it is interesting to see nearly a 42-point difference in point totals for the Sweet Sixteen games. Houston scored 78 in the first round and 88 in the second round, averaging 84 points per game so far. Illinois went off for 105 points in the first round, but came back down to Earth with 76 in the second, averaging about 90 points per game through two games. 

Both teams have talented defenses that have allowed an average of 52 points (Houston) and 63 points (Illinois) through two games. This game isn't expected to be 100-95 or anything crazy, but to reach 140 points, which would clear the over, we would just need a game where a team wins 71-69. With both teams averaging over 80 points per game on offense this tournament so far, even stout defenses are liable to allow at least 70 points. At this low of a line, the over is too good to pass up. 

MORE: Ranking the remaining Sweet 16 teams and their chance to win the championship

No. 4 Alabama (+10.5) vs. No. 1 Michigan

Michigan lost its conference tournament to Purdue and has been playing like it was personally offended by the loss. The Wolverines beat Howard by 21 in the first round and then Saint Louis by 23 in the second. Michigan has been a blue and maize buzzsaw through two rounds, but they should run into slightly more opposition in No. 4 Alabama. 

The Crimson Tide won by 20 in the first round and then beat No. 5 Texas Tech by 25 points in the second round. With how hot Michigan is, Alabama feels just as hot. Taking the Crimson Tide to outright win is way riskier, but Alabama has shown enough through two rounds of the tournament that they are a good enough bet to cover the double-digit spread. 

MORE: Tracking 2026 March Madness records by conference

No. 3 Michigan State vs. No. 2 UConn (-2.5) 

The Sweet Sixteen matchups all look fun. There are storylines woven between all of the matchups, and Michigan State taking on UConn is no different. Tom Izzo and Dan Hurley are two of the most successful coaches in the NCAA Tournament, and they will square off in this game. 

Michigan State steam rolled North Dakota State in the first round and beat Louisville by eight in the second round. UConn struggled in the first, beating No. 15 Furman by only nine, but then made adjustments against No. 7 UCLA and beat the Bruins by 16. 

Each team is entering this game with momentum. This should be one of the better games in the round, but UConn's depth and size will give it the slight advantage. Even though this spread is close, the only ways that the Huskies don't cover are if they lose, win by one point or win by two. UConn should be able to pick up the win, and even in a close game, should be able to make it by at least three points if the game comes down to free throws. 

MORE: Big Ten sets its conference record for most teams to make Sweet Sixteen

No. 6 Tennessee vs. No. 2 Iowa State: Over 138.5 points

Similar to Houston and Illinois, this point spread is too low to pass up. Iowa State is averaging 95 points through two games, and Tennessee is averaging 78.5. The Cyclone and Volunteers defenses have been solid so far, allowing just 67.5 points (Iowa State) and 64 points (Tennessee) per game so far. 

Iowa State scored an average of 82.5 points this season, while Tennessee scored 79.4 points per game. If the offenses just average their games, the point total for this one will clear 160 points, giving a betting buffer of 21 points for the over to hit, and that is just if the offenses have their average games. 

If you look at how their opponents have fared, they are allowing a combined average of 67.2 points. Assuming that they both are defensive stalwarts in the game, they would each allow 67 points in the game, which falls only five points shy of hitting the over. 

All of this math to say, barring an uncharacteristically low scoring game from the run these two teams have been on in this tournament so far, the over should safely hit. 

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