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The 5 vs. 12 matchup will get plenty of attention for 2025 March Madness upsets, but you shouldn't overlook the 6 vs. 11 matchup either. Last year, 11-seeds went 3-1 against 6-seeds, and this year's 11-seeds are comprised of a pair of First Four winners and two mid-majors. Drake will take on 6-seed Missouri in the West Region of the NCAA Tournament 2025, while VCU will face No. 6 BYU in the East Region of the 2025 NCAA bracket. The Drake Bulldogs prevent opponents from scoring and lead the nation in points allowed per game (58.4). As for VCU, its seven tournaments wins as an 11-seed or worse are the second-most in NCAA history. Was last year's success of 11 seeds an outlier, or should you expect it to continue in the 2025 March Madness bracket? Before you make your 2025 NCAA Tournament predictions, see the March Madness bracket picks from the proven computer model at SportsLine.

Last year, SportsLine's computer simulation nailed massive upsets, including huge wins by No. 11 Oregon over No. 6 South Carolina, No. 11 NC State over No. 6 Texas Tech, No. 10 Colorado over No. 7 Florida, and No. 12 James Madison over No. 5 Wisconsin last year. The model has beaten over 91 percent of all CBS Sports bracket players in four of the past six tournaments.

This model, which simulates every game 10,000 times, has nailed 24 first-round upsets by double-digit seeds since its inception in 2016 and nailed UConn's championship run last year. It nailed 13 teams in the Sweet 16 and was all over Alabama's Cinderella run to the Final Four as a 4-seed.

Now, SportsLine's advanced computer model has simulated the entire 2025 March Madness bracket 10,000 times to come up with the perfect 2025 NCAA Tournament bracket and find out which teams will pull off the biggest upsets. You shouldn't even think about making a pick without seeing what their model has to say.

Top 2025 March Madness bracket upset picks

One South Region surprise the model has identified: First Four winner North Carolina knocks off No. 6 Ole Miss in the first round. Playing in the First Four makes for a longer NCAA Tournament grind, but we've seen on multiple occasions that playing on Tuesday or Wednesday as one of the last four teams in can also help build momentum. VCU (2011) and UCLA (2021) both managed to stage Final Four runs after winning their First Four games and a First Four team has gone on to win at least one additional NCAA Tournament game every year but one since the field expanded to 68 teams in 2011.

The Tar Heels looked dynamic offensively against one of the best defensive teams in the country on Tuesday, beating San Diego State, 95-68, while shooting 52.6% from the floor and going 14-of-24 from the 3-point line. Ole Miss ranks 23rd in the nation in adjusted defensive efficiency this season, but has given up at least 76 points in eight of its last nine games. RJ Davis scored 26 points in the win over SDSU and the model expects him to be a big reason why the Tar Heels keep it rolling with an upset in the first round.

Another South Region surprise the model has identified: Creighton beats Louisville in the all-important 8-9 matchup. This game will take place at Rupp Arena, home of the Kentucky Wildcats in Lexington, Ky. It is less than 80 miles from Louisville's campus, but the Cardinals have lost eight straight regular-season road games at Rupp Arena. Additionally, first-year Louisville coach Pat Kelsey is 0-4 all-time in the NCAA Tournament, going winless in previous stops at Winthrop (0-2) and College of Charleston (0-2).

Creighton has much brighter prospects for 2025 March Madness as it's one of five D1 teams to win at least one NCAA tourney game in each of the past four seasons. The Bluejays will also have the best player on the floor in 7-foot center Ryan Kalkbrenner. He averages 19.4 points, after putting up 18.7 points across three NCAA tourney games a year ago, but offense isn't even his strength. He and Patrick Ewing are the only four-time Big East Defensive Player of the Year winners, and Kalkbrenner should present problems for a Louisville team whose top four scorers check in at 6-foot-6 or shorter. See which other 2025 March Madness matchups to target here.

How to make 2025 NCAA Tournament bracket predictions

Who wins every tournament-defining matchup? And which teams will make surprising runs through the 2025 NCAA Tournament bracket? With the model's track record of calling bracket-busting upsets, you'll want to see which stunners it's calling this year before locking in any 2025 NCAA bracket picks.

So what's the optimal NCAA Tournament 2025 bracket? And which NCAA Tournament Cinderella teams will shock college basketball? Visit SportsLine now to see which region features two mammoth upsets in the first round, including one by a team that's only ever won a single tournament game, and see which 6-seed makes the Sweet 16, all from the model that's nailed 24 first-round upsets by double-digit seeds.