March Madness best bets & upset picks for today's first-round games: Vanderbilt, Kentucky, Oklahoma among Friday's plays

Ahead of nearly 12 hours straight of hoops action, we have our March Madness best bets and upset picks for Friday, March 21.

Best bets and upset picks for today's first-round March Madness action 

Here are five picks to consider on Friday's NCAA Tournament games: 

NCAA Tournament upset pick of the day: 10 Vanderbilt (+160 moneyline) vs. No. 7 Saint Mary's, 3:15 p.m. ET | truTV

Our favorite upset pick for Friday's first-round games is Vanderbilt over Saint Mary's. The Commodores came through a tough SEC schedule, which has them ready for any opponent. Saint Mary's likes to play slow, as slow as any team in the country. That has worked this season as they have been able to dictate the pace, but it may be harder against a more talented and athletic Vanderbilt team.

Jason Edwards is scoring 17 points a game for Vanderbilt, and point guard AJ Hoggard is scoring 9.8 PPG and dishing out 4.6 APG.

This contest will be close for most of it, but at some point in the second half, Vanderbilt will go on a run and take a multi-possession lead. With the pace that Saint Marys plays at, it will be too much to overcome, and the Commodores will pull off the upset.

Small upset in the West: No. 5 Memphis +104 moneyline vs. No. 12 Colorado State, 2 p.m. ET | TBS

This has been one of the more confusing lines for the first round of the NCAA Tournament. Colorado State opened as the favorite, even though the Rams are seven seed lines lower than Memphis. A big reason for this is the questionable status of two of Memphis' guards, Tyrese Hunter (13.7 PPG) and Dante Harris (2.4 PPG). While missing one or both players would be a blow, the Tigers should still win their first-round game.

The Tigers still have PJ Haggerty, who ranks third in the nation for scoring at 21.8 points per game. He is more than capable of carrying the Tigers when he needs to, and he did that in the AAC Tournament. Memphis' closest game was their quarterfinal win over Wichita State (83-80), and Haggerty dropped 42 points, nine rebounds, and four assists in an incredible performance. 

March Madness best bet: No. Kentucky -11.5 (-105) vs. 14 Troy , 7:10 p.m. ET | CBS 

The Wildcats have been up and down during Mark Pope's first season but play in one of the strongest conferences in the history of college basketball. The grind of the SEC should have them ready for a solid NCAA Tournament run. They finished the season playing their best basketball, too, winning four of their last six. The two losses came to top-five ranked teams.  

They also tend to cover the spread when they win, as they have cashed for bettors in 15 of their 22 wins. They also have covered and won in three straight games where they have been favored by seven more points. Troy is a solid team but has covered once all season when they were 10+ point underdogs. This game will be close for a half, but Kentucky will pull away in the second half to win by 15+.

Best bet: No. 13 Akron +14.5 (-108) vs. No. 4 Arizona, 7:35 p.m. ET | truTV

Arizona has been up and down all season. With a 22-12 record, the Wildcats are seeded a line or two better than they deserve. Meanwhile, Akron, at 28-6, was underserved by a line or two. The Zips had an average start to the season, but when the calendar flipped to 2025, Akron started clicking and has played its best basketball, going 21-1 in the New Year.

The Wildcats finished the season winning only five of their last 11 games, covering the spread just four times in that run. Akron, though, has covered four of its last six games and its last two as an underdog. The two players to watch on Akron are Tavari Johnson (13 PPG), who scored 15 points in his last two games, and Nate Johnson (14 PPG), who is incredibly hot, scoring 31 and 22 in his last two games. 

Best bet: No. 9 Oklahoma +5.5 (-110) vs. No. 8 UConn, 9:25 p.m. ET | TNT

The Huskies have underwhelmed this season after winning two straight national championships. They look like a team without an identity and often search for a go-to guy in late-game situations. Two seasons ago, Jordan Hawkins and Tristen Newton hit tons of clutch shots, and then last year, they still had Newton along with Cam Spencer and freshman Stephon Castle.

This season, they have looked to players like Solo Ball and Liam McNeeley but have not delivered at the same level. Oklahoma has had to fight through an absolute gauntlet of an SEC schedule and, in the process, found a superstar freshman in Jeremiah Fears. Fears is averaging 17 PPG and is coming off an SEC Tournament where he averaged 28.5 PPG. UConn has the upper hand in this matchup, but Oklahoma has not been defeated by more than three points in its seven straight games. The Sooners have a great chance to pull an upset and will at least cover.