Sweet 16 best bets: Full analysis, picks against the spread

The Sweet 16 is set to begin on Thursday night with Clemson taking on Arizona in the first game of the round.

The first 2 rounds of the NCAA Tournament were exciting as always, but they only produced a couple of major upsets. Every No. 1 and No. 2 seed made it into the second weekend of the Big Dance.

Favorites were particularly profitable in the round of 32 when they went 15-1 straight up and 11-5 against the spread. That’s something to keep in mind as the Sweet 16 tips off on Thursday night.

Here are my against-the-spread picks for the Sweet 16:

Note: All spreads via Bet365 unless otherwise noted:

Thursday, March 28

6 Clemson vs. 2 Arizona | 7:09 p.m. ET | Los Angeles, California | CBS

Spread: Arizona -7

Clemson needed 2 upsets — and a lot of shooting luck — to get to this game. New Mexico and Baylor shot just 19% from 3-point range against the Tigers last weekend, and I’m not sure that kind of luck is going to continue in this spot against Arizona.

However, the Wildcats have struggled a bit more down the stretch and even appeared to be on the ropes a little bit vs. Long Beach State in the first round. According to EvanMiya’s relative ratings index, Clemson has performed at an elite level vs. the best teams in the country this season. I think Arizona will probably end up winning this game, but I like Clemson to keep it close.

Pick: Clemson +7.5 (via FanDuel)

5 San Diego State vs. 1 UConn | 7:39 p.m. ET | Boston, Massachusetts | TBS/truTV

Spread: UConn -11

UConn has looked like a buzz-saw pretty much since the start of last year’s NCAA Tournament. The Huskies have now won 8 straight NCAA Tournament games by double digits dating back to last year’s title run, and Vegas is expecting that streak to continue vs. SDSU. Of course, this game against the Aztecs will be a rematch of last year’s national title game, which UConn won 76-59.

Ultimately, I think this is too many points for the Huskies. San Diego State has the No. 8 defense in the country according to KenPom’s efficiency metric, which should allow the Aztecs to keep this game within single digits.

Pick: San Diego State +11

4 Alabama vs. 1 North Carolina | After Clemson/Arizona game | Los Angeles, California | CBS

Spread: North Carolina -4

North Carolina enters this game on a hot streak, having won 10 of its last 11 games overall. Alabama struggled down the stretch of the season and needed a late charge to get past Grand Canyon in the round of 32.

Alabama’s defense is a big weakness. Since Feb. 1, the Tide’s defense ranks 141st nationally per BartTorvik’s defensive efficiency rankings. I’m not moved by Alabama’s 86.5 defensive rating against Grand Canyon — the Lopes made it easy on Alabama by choosing to not run any sets. North Carolina plays with structure, which is something the Tide have not handled well this season. It’s hard to imagine betting on Alabama in this spot given its struggles on that end of the floor.

Pick: North Carolina -3.5 (via FanDuel)

3 Illinois vs. 2 Iowa State | After San Diego State/UConn game | Boston, Massachusetts | TBS/truTV

Spread: Iowa State -1.5

Like Alabama, Illinois has also struggled mightily on the defensive end lately. But unlike Alabama, Illinois has one of the best scorers in the country in Terrance Shannon Jr. to make up for it. Shannon has scored 25+ points in 6 straight games and is averaging 27.1 points per game since Feb. 10.

Shannon and Illinois’ offense will be put to the test against Iowa State, who owns the nation’s No. 1 defense according to KenPom. It’s been more than a month since Iowa State gave up more than 1 point per possession (which last happened against Houston on Feb. 19). It’s tempting to take the elite offense, but I’m siding with the Cyclones in this spot.

Pick: Iowa State -1.5

Friday, March 29

11 NC State vs. 2 Marquette | 7:09 p.m. ET | Dallas, Texas | CBS

Spread: Marquette -6.5

Marquette battled some injury woes down the stretch of the season, but things appear to be coming together at the right time for the Golden Eagles. Marquette got past a really good Colorado team in the round of 32 and now has an opportunity to get to the Elite Eight without facing a single-digit seed.

NC State needed a miracle run at the ACC Tournament to even reach the Big Dance, and now finds itself in the Sweet 16 after winning a couple more close games. I think this is where NC State’s Cinderella story comes to an end — Marquette is too good and too ruthless to allow it to continue. I like the Golden Eagles by double digits.

Pick: Marquette -6.5

5 Gonzaga vs. 1 Purdue | 7:39 p.m. ET | Detroit, Michigan | TBS/truTV

Spread: Purdue -5.5

This is an Elite Eight-quality game taking place in the Sweet 16. Gonzaga is a 5-seed, but the Bulldogs will enter this game as the No. 12 team in the country, per KenPom’s rankings. They haven’t lost to anyone besides Saint Mary’s since Jan. 11. They have good enough guard play to punish Purdue’s drop coverage. Gonzaga also has plenty of size to throw at Zach Edey and has no obvious weaknesses on either side of the ball. I see this as pretty close to a matchup nightmare for the Boilermakers and will gladly take the points with Gonzaga.

Pick: Gonzaga +5.5

4 Duke vs. 1 Houston | After NC State/Marquette game | Dallas, Texas | CBS

Spread: Houston -4

Houston needed overtime to avoid an epic collapse against Texas A&M in the round of 32. Meanwhile, Duke took care of business in dominant fashion over the weekend with big wins over Vermont and James Madison. Houston will be a different kind of test, however, as the Blue Devils will go from facing double-digit seeds to one of the very best teams in the country. Houston proved itself over and over again in a tough Big 12 this season, and I’m backing the Cougars to make a statement against Duke in this spot.

Pick: Houston -3.5 (via BetMGM)

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3 Creighton vs. 2 Tennessee | After Gonzaga/Purdue game | Detroit, Michigan | TBS/truTV

Spread: Tennessee -3

These teams are pretty close in terms of quality, but only one of them has Dalton Knecht. The All-American was quiet against Texas — which almost cost the Vols their season — but I think he’ll be ready to go in the Sweet 16 against Creighton. The Blue Jays are amongst the worst teams in the entire country in terms of forcing turnovers and getting to the foul line. Creighton’s offense generates nearly 40% of its offense from behind the 3-point line, and the Vols had a top-30 3-point percentage defense nationally in 2023-24. This doesn’t seem like a great matchup for the Blue Jays.

Pick: Tennessee -2.5 (via FanDuel)