Biggest NCAA tournament point-spread upsets of the 64-team era

16-seed UMBC Retrievers guard Jairus Lyles celebrates beating 1-seed Virginia Cavaliers in the first round of the 2018 NCAA Tournament. Peter Casey-USA TODAY Sports

While double-digit seeds always win games in the NCAA tournament, which upsets were the largest from a Vegas perspective?

Since the NCAA tournament expanded to 64 teams in 1985, there have been 46 double-digit upsets based on the point spread. Below are the largest in that span.

1. March 16, 2012 -- round of 64

No. 15 Norfolk State Spartans vs. No. 2 Missouri Tigers

Closing line: Missouri -21.5

The biggest tournament upset win in the 64-team era belongs to Norfolk State, which defied the 21.5-point spread and shocked Missouri. The Spartans were led by Kyle O'Quinn, who scored a game-high 26 points to go along with 14 rebounds. Up two with 3.8 seconds left, O'Quinn, despite his great game, missed two free throws and opened the door for the Tigers. Phil Pressey, however, missed a potential game-winning 3-pointer at the buzzer, and Norfolk State had officially shocked the college basketball world.

It turned out to be one of two wins by a 15-seed over a 2-seed that day -- the only time that has happened in tournament history -- as No. 15 Lehigh beat No. 2 Duke as a 12-point underdog.

Final score: Norfolk State 86, Missouri 84

2. March 16, 2018 -- round of 64

No. 16 UMBC Retrievers vs. No. 1 Virginia Cavaliers

Closing line: Virginia -20.5

While it wasn't the largest betting upset in NCAA tournament history, it was the first time in 136 tries that a 16 seed beat a 1 seed in the Big Dance. And not only did UMBC pull off the win, it beat Virginia by 20 points, making this the largest difference between winning margin and the spread by an underdog in the NCAA tournament in the 64-team era. The game was tied at 21 at halftime, but UMBC outscored Virginia 53-33 in the second half for the victory. Jairus Lyles led the way, with 23 of his 28 points coming in the second half. The Retrievers closed as a 25-to-1 underdog on the moneyline in some sportsbooks.

Final score: UMBC 74, Virginia 54

3. March 18, 1993 -- round of 64

No. 15 Santa Clara Broncos vs.No. 2 Arizona Wildcats

Closing line: Arizona -20

Santa Clara was the first 20-point upset in the 64-team era, when it shocked Damon Stoudamire and Arizona in 1993. The Broncos trailed by as many as 13 points in the second half, but Arizona shot just 25 percent in that half, allowing the Broncos to become the second 15-seed to win an NCAA tournament game. Santa Clara point guard Steve Nash had 10 points, but Pete Eisenrich's 19 points fueled the upset win.

Final score: Santa Clara 64, Arizona 61

4. March 14, 1997 -- round of 64

No. 15 Coppin State Eagles vs. No. 2 South Carolina Gamecocks

Closing line: South Carolina -18.5

Coppin State became the third-ever 15-seed to win a tournament game, as the Eagles stunned SEC regular-season champion South Carolina. The game was tied at halftime, and South Carolina opened up a seven-point lead in the second half. After that, Coppin State outscored South Carolina 38-18 in the final 13 minutes to win by 13. The margin of victory remains the largest by a 15-seed in a tournament game. It was also the first tournament win for both Coppin State and the MEAC conference as a whole.

Final score: Coppin State 78, South Carolina 65

T-5. March 15, 2001 -- round of 64

No. 15 Hampton Pirates vs. No. 2 Iowa State Cyclones

Closing line: Iowa State -17.5

Despite coming off an early exit in the Big 12 tournament, Iowa State was expected to roll over Hampton. The game marked the first tournament appearance for the Pirates, who were in their sixth season as a Division I program. Hampton's Tarvis Williams put his team up one with 6.9 seconds left, and Iowa State's Jamaal Tinsley missed a layup at the buzzer. The Pirates pulled the upset despite shooting 38.9 percent from the field and 15 percent from 3.

Final score: Hampton 58, Iowa State 57

T-5. March 14, 1986 -- round of 64

No. 14 Little Rock Trojans vs.No. 3 Notre Dame Fighting Irish

Closing line: Notre Dame -17.5

Notre Dame had no answer for Arkansas-Little Rock defensively, as the Fighting Irish allowed a season-high 90 points. Three players scored at least 20 points for the Trojans, led by Pete Myers' 29 points. They were even better in the second half when they shot 79 percent from the field. This was also the first upset by a 14-seed in the NCAA tournament.

Final score: Arkansas-Little Rock 90, Notre Dame 83

7. March 18, 2016 -- round of 64

No. 15 Middle Tennessee Blue Raiders vs. No. 2 Michigan State Spartans

Closing line: Michigan State -16.5

After winning the Big Ten conference tournament, big things were expected from Denzel Valentine and Michigan State. But in the shocker of the 2016 NCAA tournament, Middle Tennessee led throughout and knocked off the heavily-favored Spartans. Incredibly, Michigan State lost despite shooting 55.6 percent from the field, its sixth-best field goal percentage in an NCAA tourney game under Tom Izzo. The Spartans were a -9000 favorite.

Final score: Middle Tennessee 90, Michigan State 81

T-8. March 19, 2015 -- round of 64

No. 14 UAB Blazers vs. No. 3 Iowa State Cyclones

Closing line: Iowa State -14

Fourteen seasons after being stunned by Hampton, another highly seeded Iowa State team fell as a double-digit favorite in the round of 64. The Cyclones had an early 10-point lead, but in the second half neither team could get a lead of more than four points. The Blazers closed the game on a 9-4 run in the final 1 minute, 40 seconds to win by one. It was the second time in 12 seasons that they won a tournament game as a double-digit underdog; UAB beat top-seed Kentucky as a 10-point underdog in 2004.

Final score: UAB 60, Iowa State 59

T-8. March 22, 2013 -- round of 64

No. 15 Florida Gulf Coast Eagles vs. No. 2 Georgetown Hoyas

Closing line: Georgetown -14

Georgetown lost as a double-digit favorite in the tournament for the second time in four years -- this time at the hands of Florida Gulf Coast. The Eagles were making their first tournament appearance in just their second year of eligibility. After Florida Gulf Coast led 24-22 at halftime, "Dunk City" came alive in the second half, as the Eagles scored 54 points en route to a 10-point win. How unlikely was the Eagles' 54-point second half? Georgetown entered the tournament allowing just 55.7 points per game.

Final score: Florida Gulf Coast 78, Georgetown 68

T-8. March 12, 1987 -- round of 64

No. 14 Austin Peay Governors vs.No. 3 Illinois Fighting Illini

Closing line: Illinois -14

After Illinois hit a shot to take a one-point lead with just 13 seconds left, Austin Peay's Tony Raye drew a foul on a layup attempt with two seconds remaining. Despite being a 56 percent free throw shooter on the year, he hit both shots and Austin Peay held on for the upset victory. Austin Peay nearly pulled off another upset in the next round against Providence as a 7.5-point underdog but fell 90-87 in overtime.

Final score: Austin Peay 68, Illinois 67

T-11. March 18, 2010 -- round of 64

No. 14 Ohio Bobcats vs. No. 3 Georgetown Hoyas

Closing line: Georgetown -13.5

This one was never in doubt. The Bobcats' starting backcourt of D.J. Cooper and Armon Bassett combined for 55 points as they dominated the favored Hoyas. They led 48-36 at halftime and held a lead of at least seven points for the entire second half. Their 97 points remain the most ever by a team seeded 13th or lower in the tournament.

Final score: Ohio 97, Georgetown 83

T-12. March 18, 2005 -- round of 64

No. 14 Bucknell Bison vs. No. 3 Kansas Jayhawks

Closing line: Kansas -13.5

This upset was more than just a 13.5-point spread -- it pitted one of college basketball's blue bloods against a small school in central Pennsylvania. Kansas was the preseason No. 1 going into the 2004-05 season, and it had won at least one game in each of its previous 15 tournaments. Bucknell, on the other hand, had lost its only two tournament games in school history by an average of 27.5 points. None of that mattered on this Friday night in Oklahoma City. The Bison's Chris McNaughton rattled in a hook shot with 10.5 seconds left, and Bucknell survived a pair of potential game-winners from Kansas to pull off the shocker.

Final score: Bucknell 64, Kansas 63

T-13. March 16, 1990 -- round of 64

No. 14 Northern Iowa Panthers vs. No. 3 Missouri Tigers

Closing line: Missouri -13.5

Missouri trailed by 12 points with less than five minutes left, but came back to tie it at 71. Northern Iowa called a timeout with 10 seconds left and substituted 3-point specialist Maurice Newby into the game. Newby got the ball after a dribble handoff and hit a long 3-pointer to give the Panthers the upset victory.

It wouldn't be the only time Northern Iowa pulled off a double-digit upset. In the 2010 round of 32, Ali Farokhmanesh and the Panthers shocked top-seed Kansas as an 11.5-point underdog.

Final score: Northern Iowa 74, Missouri 71

T-14. March 21, 2014 -- round of 64

No. 14 Mercer Bears vs. No. 3 Duke Blue Devils

Closing line: Duke -13

For the second time in three seasons, Duke was upset as a double-digit round-of-64 favorite. In 2012, C.J. McCollum and Lehigh beat Duke as a 12-point underdog. This time, it was Atlantic Sun Conference champion Mercer knocking off Duke. The Bears came back from five points down with 4:40 to go, finishing the game on a 20-8 run. It was the second straight season the Atlantic Sun champion won as a big underdog, after Florida Gulf Coast's victory over Georgetown in 2013.

Final score: Mercer 78, Duke 71

T-14. March 21, 2002 -- Sweet 16

No. 5 Indiana Hoosiers vs. No. 1 Duke Blue Devils

Closing line: Duke -13

In the only Sweet 16 game to make the list, Indiana overcame a 17-point deficit to beat defending champion Duke in a wild game. It appeared over when Indiana took a four-point lead with 11.1 seconds left, but on the ensuing possession, Duke's Jay Williams was fouled while making a 3-pointer with 4.2 seconds left. He missed the free throw, though, and the Hoosiers pulled off the massive upset.

Final score: Indiana 74, Duke 73

T-14. March 16, 2018 -- round of 64

No. 13 Marshall Thundering Herd vs. No. 4 Wichita State Shockers

Closing line: Wichita State -13

Marshall kept it close all game before pulling away late in the second half for the upset victory. The Thundering Herd shot 46.7 percent from the field and scored 47 points in the second half for the win. They were led by Jon Elmore, who scored 27 points.

Final score: Marshall 81, Wichita State 75