The Mountain Hawks were the sixth 15 seed overall to pull off the trick. Norfolk State edged Missouri in the West Regional earlier in the day, and No. 13 seed Ohio knocked off fourth-seeded Michigan to add to the madness.
Duke dropped its first tournament game for only the second time in the past 16 years, and this one occurred just 88.5 kilometres from its campus. Coach Mike Krzyzewski and the Blue Devils also lost their opener against 11th-seeded Virginia Commonwealth in 2007.
Duke (27-7) had no answer for McCollum, a speedy guard who's a two-time Patriot League player of the year and the nation's fifth-leading scorer.
It didn't help that the Blue Devils shot 6 of 26 from three-point range.
Lehigh (27-7) led most of the game, drawing support from North Carolina fans who borrowed brown signs from Mountain Hawks supporters that read "Go Lehigh" to root against their rivals.
The Patriot League champions led most of the first half despite shooting just 38 per cent from the field and grabbed the lead for good at the 8:21 mark of the second half when Mackey McKnight made a three-pointer.
No. 10 XAVIER 67, No. 7 NOTRE DAME 63
Tu Holloway banked in the go-ahead shot over Jack Cooley with 21.3 seconds left, helping Xavier rally for the win.
Holloway finished with 25 points on 10-for-15 shooting, including a flurry that helped the 10th-seeded Musketeers (22-12) rally from a 10-point second-half deficit against the seventh-seeded Fighting Irish (22-12). His final points came when he rounded a screen from Kenny Frease and sent a high-arcing shot over Cooley's outstretched arm for the 64-63 lead.
Cooley finished with 18 points on 8-for-8 shooting for the Fighting Irish, who couldn't slow Holloway in the second half.
Dezmine Wells finished with 14 points and 11 rebounds for Xavier, which will play No. 15 seed Lehigh in Sunday's third round.
No. 15 NORFOLK STATE 86, No. 2 MISSOURI 84
OMAHA, Neb. (AP) — Kyle O'Quinn had 26 points and 14 rebounds, making several key plays in the closing minutes, and Norfolk State held on to stun Missouri.
Pendarvis Williams and Chris McEachin each added 20 points for the MEAC champion Spartans (26-9), who made their first trip to the NCAA tournament a memorable one. They became the first No. 15 seed to beat a No. 2 since fellow conference member Hampton knocked off Iowa State in 2001.
O'Quinn had a chance to take some of the drama out of the finish when he went to the free throw line with 3.8 seconds to go, but the 70-per cent foul shooter missed both tries.
Missouri coach Frank Haith called a timeout with 2.9 seconds left to set up a final play, and the ball wound up in the hands of Phil Pressey. He took a couple of hard dribbles and let loose a three-pointer from the wing that clanked off the back iron as the buzzer sounded.
Norfolk State advanced to play No. 7 seed Florida in the third round Sunday.
Michael Dixon led Big 12 tournament champion Missouri (30-5) with 22 points, and Pressey and fellow guard Marcus Denmon finished with 20 points each. Pressey also had eight assists.
No. 7 FLORIDA 71, No. 10 VIRGINIA 45
Bradley Beal had 14 points and 11 rebounds, reserve Casey Prather scored a career-high 14 and Florida pulled away in the second half to beat Virginia.
The Gators (24-10) finished the first half on a 17-4 run to shake off a slow start and get out to a 30-22 lead. They shot 70 per cent in the second half, pushing their lead to more than 20 points.
Florida made it to the regional finals last season. The Cavaliers were in the tournament for the first time since 2007.
Mike Scott had 15 points for Virginia (22-10).
Florida, averaging a nation-leading 9.9 3-pointers a game, was 4 of 23 from long range but made 24 of 30 from inside the arc.
No. 1 MICHIGAN STATE 89, No. 16 LIU BROOKLYN 67
COLUMBUS, Ohio (AP) — Draymond Green scored 24 points in a triple-double and top-seeded Michigan State fought off the upset bug that took down two No. 2 seeds in the NCAA tournament.
The Spartans (28-7) finally put away the pesky No. 16 Blackbirds (25-9) with a 14-4 run midway through the second half.
Michigan State will play Saint Louis in the third round Sunday.
Green added 12 rebounds and 10 assists. The Big Ten's player of the year also provided some encouraging — and a few choice — words for his teammates in the second half when LIU was giving the Spartans all they could handle.
Jamal Olasewere scored 17 for LIU.
No. 9 SAINT LOUIS 61, No. 8 MEMPHIS 54
COLUMBUS, Ohio (AP) — Kwamain Mitchell scored 22 points, including three big 3-pointers, and Saint Louis rode its gritty defence to a victory over Memphis.
Mitchell closed the first half by banking in a three, then nailed two others to help coach Rick Majerus and the Billikens (26-7) overturn an eight-point deficit in the second half. They moved on to play the winner of LIU Brooklyn and top-seeded Michigan State on Sunday.
Brian Conklin added 16 points, including five free throws in the final minute to salt the game away.
Will Barton had 16 points for the Tigers (26-9), who had won 20 of their last 23 games.
No. 3 FLORIDA STATE 66, No. 14 ST. BONAVENTURE 63
NASHVILLE, Tenn. (AP) — Bernard James scored 19 points and Florida State barely avoided a big upset, rallying to beat St. Bonaventure.
The Seminoles (25-9) shook off a slow start and won their sixth straight game, including their run to the Atlantic Coast Conference championship last week. They will play sixth-seeded Cincinnati on Sunday in the third round.
Toronto's Andrew Nicholson scored 20 points and Demetrius Conger had 14 for St. Bonaventure (20-12), which was trying to win an NCAA tournament game for the first time since 1970.
Florida State used a 16-2 run to take its first lead with 5:15 left on a three-pointer by Ian Miller. The Seminoles led as much as 60-52 on a dunk by Okaro White with 2:47 left, but had to hold on at the end.
No. 6 CINCINNATI 65, No. 11 TEXAS 59
NASHVILLE, Tenn. (AP) — Yancy Gates had 15 points and 10 rebounds as Cincinnati started strong and then withstood a late rally by Texas.
The Bearcats (25-10) jumped out to a 16-2 lead while Texas opened the game 1 of 14 from the field and shot 16 per cent for the first half. After trailing 31-17 at halftime, the Longhorns attacked, hitting five of their first seven from three-point range.
With 3:44 to play, Texas' Jonathan Holmes made a layup to tie it at 52, but the Longhorns never took the lead. Gates hit a shot over Clint Chapman with 1:11 remaining to give Cincinnati a 58-52 cushion, and the Bearcats hit five free throws in the final 36 seconds.
J'Covan Brown led Texas (20-14) with 19 points. Chapman had 10 points and 14 rebounds.
Myck Kabongo of Toronto, the Longhorns' starting point guard, had four steals and a pair of assists, and finished with just two points on 0-for-6 shooting.
No. 1 NORTH CAROLINA 77, No. 16 VERMONT 58
Tyler Zeller had 17 points and 15 rebounds to help North Carolina beat Vermont in its NCAA tournament opener despite playing without injured starter John Henson.
Freshman forward James Michael McAdoo added a season-high 17 points for the Tar Heels (30-5), who pushed ahead by double figures late in the first half and then broke the game open after halftime. They improved to 30-1 in NCAA tournament games played in their home state.
Sandro Carissimo had 11 points for the Catamounts (24-12), who beat Lamar in one of Wednesday's First Four games. That earned them a trip to Greensboro to face the Tar Heels in front of a home-state crowd wearing plenty of light blue.
The Tar Heels didn't turn in a rousing performance, but they had a danger-free afternoon and advanced to play eighth-seeded Creighton on Sunday. They also bought Henson another two days to recover from that sprained left wrist. The six-foot-10 junior was hurt during last week's Atlantic Coast Conference tournament and missed the last two games in Atlanta.
No. 8 CREIGHTON 58, No. 9 ALABAMA 57
Doug McDermott scored 16 points and Creighton overcame an 11-point deficit in the second half to beat Alabama for its first NCAA tournament victory in 10 years.
Ottawa's Jahenns Manigat had six points, two rebounds and an assist for Creighton.
Alabama had a chance to win during the frantic final seconds, but Josh Jones blocked Trevor Releford's three-point attempt from the top of the key as time expired.
McDermott, the MVP of the Missouri Valley Conference and the nation's third-leading scorer at 23.2 points per game, was held scoreless for more than 14 minutes but then scored nine points down the stretch for the Bluejays (29-5).
It was Creighton's first tournament victory since Terrell Taylor drilled a three-pointer with 0.2 seconds left in double overtime to lift the Bluejays to an upset win over Florida in 2002.
Releford led Alabama (21-12) with 14 points and Trevor Lacey added 13.
No. 13 OHIO 65, No. 4 MICHIGAN 60
NASHVILLE, Tenn. (AP) — D.J. Cooper scored 21 points and Ohio held off Michigan for yet another second-round upset in the NCAA tournament.
The underdog Bobcats (28-7) had the Wolverines on their heels throughout the game, but Trey Burke hit a three-pointer with 4:12 left to cut it to 63-60. Michigan then missed its final five shots, four by Burke.
Michigan (24-10) got the rebound on Burke's third miss, a three-point attempt with 22 seconds left, but Evan Smotrycz lost control of the ball and Walter Offutt grabbed it. He was fouled by Smotrycz and sank both free throws with 6.8 seconds left to seal it.
Ohio shot 51.2 per cent and held Michigan to 40.7 per cent shooting, including 7 for 23 from 3-point range — typically the Wolverines' comfort zone. Burke finished with 16 points.
No. 12 SOUTH FLORIDA 58, No. 5 TEMPLE 44
NASHVILLE, Tenn. (AP) — Victor Rudd Jr. and Anthony Collins each scored 17 points, and South Florida shook off a frigid first 20 minutes to earn the upset.
The 12th-seeded Bulls (22-13) took it to the Atlantic 10 regular-season champ with their bruising Big East-style of play and held Temple 20 points below its previous season low in scoring.
That allowed the Bulls, who beat California 65-54 in Dayton on Wednesday night, to overcome a first half in which they went nearly 16 minutes without a field goal and missed 22 straight. They will play No. 13 seed Ohio, on Sunday.
Khalif Wyatt led Temple (24-8) with 19 points.
No. 3 GEORGETOWN 74, No. 14 BELMONT 59
COLUMBUS, Ohio (AP) — Jason Clark scored 21 points, Otto Porter added 16 and Georgetown's ruthless defence bottled up Belmont's shooters, sending the Hoyas into the next round of the NCAA tournament after early exits the past two years.
Henry Sims had 15 points for the Hoyas (24-8), who shot 62 per cent from the floor and will play No. 11 seed North Carolina State in the third round Sunday.
Georgetown's previous two seasons ended with embarrassing first-round losses to Virginia Commonwealth and Ohio. The Hoyas weren't going to let that happen a third time to a pesky underdog.
The Bruins (27-8) had their 14-game winning streak stopped and fell to 0-5 in NCAA appearances.
Blake Jenkins scored 17 to lead Belmont, which went just 10 of 27 on three-pointers.
No. 11 NORTH CAROLINA STATE 79, No. 6 SAN DIEGO STATE 65
COLUMBUS, Ohio (AP) — Richard Howell scored 22 points, double his season average, and North Carolina State used its muscle inside and sticky defence to beat San Diego State.
Lorenzo Brown added 17 points and C.J. Leslie 15 for the Wolfpack (23-12), who improved to 12-5 in NCAA tournament openers. N.C. State has won at least one game in seven of its last eight trips.
Jamaal Franklin had 23 points and Chase Tapley 19 for the Aztecs (26-8), regular-season champions of the Mountain West Conference.
No. 2 KANSAS 65, DETROIT 50
OMAHA, Neb. (AP) — Thomas Robinson had 16 points and 13 rebounds, and second-seeded Kansas rolled to the victory.
Elijah Johnson added 15 points and Tyshawn Taylor had 10 for the Jayhawks (28-6), who toyed with the Titans (22-14) for the first 15 minutes before ramping up the defence and making sure they didn't accompany fellow No. 2 seeds Missouri and Duke on the way out of the NCAA tournament.
Kansas advanced to play No. 10 seed Purdue on Sunday.
Doug Anderson led the Horizon League-champion Titans with 15 points before fouling out with 11:06 left. Ray McCallum, the son of the Detroit coach, added eight on 4-for-15 shooting.
No. 10 PURDUE 72, No. 7 SAINT MARY'S 69
OMAHA, Neb. (AP) — Lewis Jackson made the go-ahead free throws for Purdue with 22.8 seconds left after Saint Mary's had rallied late from 11 points down to take its first lead.
Jorden Page hit a three-pointer with 44.2 seconds remaining to finish a 14-2 run that brought the Gaels back from a 66-55 deficit with 4:24 to play.
Purdue's Terone Johnson and Saint Mary's Clint Steindl were called for travelling before Jackson made his free throws. Page badly missed what would have been a go-ahead three with 10 seconds left, and Robbie Hummel made two free throws for a three-point lead.
Rob Jones, who had 23 points, missed a three at the buzzer for the Gaels (27-6).
Johnson had 21 points, Jackson 18 and Hummel and Anthony Johnson scored 10 apiece for the Boilermakers (22-12).