An NCAA tournament that began innocently enough started to rumble Friday afternoon and didn’t stop until two No. 2 seeds — mighty Duke and also SEC-bound Missouri — had lost.

The four-time national champion Blue Devils are gone after their first game in the NCAA tournament for only the second time in the past 16 years. Last time the culprit was Virginia Commonwealth in 2007. This time it came at the hands of No. 15-seed Lehigh 75-70 in the seemingly safe haven of the Greensboro Coliseum.

Duke figured to be a shaky No. 2 seed to begin with, but maybe Sweet 16 shaky. Not in the first round, and not in a building 55 miles from Durham where the Blue Devils had been 12-0 in NCAA tournament games.

This kind of loss doesn’t happen to coach Mike Krzyzewski, but thanks to C.J. McCollum’s 30 points and Lehigh’s first win in the NCAA tournament, his next concern is coaching the U.S. Olympic team in London.

“The game has taken me to incredible highs, and the game will also take you to incredible lows,” said Krzyzewski, who in November passed Bob Knight to become college basketball’s winningest coach, to TV reporters after the game. “That’s part of being in the game, and today is one of those incredible lows.

“The game is a beautiful game. It’s been kind to me. Tonight it wasn’t very good, but that was Lehigh’s fault. They beat us, and congratulations to them.”

He acknowledged at halftime that the Blue Devils hadn’t adjusted to the injury to forward Ryan Kelly, and they never made the adjustment to McCollum either. The nation’s fifth-leading scorer is an NBA prospect despite playing in the Patriot League. Now the world knows why.

His speed and treachery in the backcourt kept Duke guards in foul trouble throughout the game, and his 3-pointer with 2:30 to go gave Lehigh a five-point cushion, good enough to withstand a couple of too-little, too-late 3-pointers.

Lehigh was 0-for-4 in its first four NCAA tournament trips, but the Mountain Hawks kept up with a trend Friday. The NCAA tournament had gone 11 years without a No. 15 seed topping a No. 2. Lehigh and Norfolk State did it in back-to-back sessions. No. 13 seed Ohio got in on the action with a 65-60 win over No. 4 Michigan as well.

With a wink to the late Lorenzo Charles and his 1983 national-championship good fortune for N.C. State, Norfolk State’s Kyle O’Quinn turned an airball into a backside rebound for the ages.

His resulting three-point play with 34.9 seconds left helped No. 15-seed Norfolk knock off No. 2-seed Missouri 86-84 on Friday. Together Lehigh and Norfolk State joined the ranks of Hampton (2001), Coppin State (1997), Santa Clara (1993) and Richmond (1991) as the No. 15 seeds to top a No. 2 seed since the NCAA tournament field expanded in 1985.

“Coming into the game, I believed it,” said Norfolk State’s Rodney McCauley, whose baseline jumper sailed over the rim and into O’Quinn’s grasp. “I believed it from the jump. Honest to God’s truth. We’ve got good shooters. We dig deep. We’re not ready to go home yet.

“We’ve got five seniors. We’re ready to keep playing.”

Norfolk State of the Mid-Eastern Athletic Conference was playing in its first NCAA tournament, and by upsetting Missouri (30-5) claimed its first win in 11 tries against a ranked opponent.

Behind O’Quinn’s 26 points and 14 rebounds and a Phil Pressey miss at the buzzer for Missouri, the tournament had its first moment, something both Florida State and Creighton avoided earlier in the day on last-second blocked shots by Bernard James and Josh Jones, respectively.

Five ACC teams entered the tournament fray Friday and only FSU, N.C. State and top-seeded North Carolina emerged.

The Tar Heels opened the tournament without ACC defensive player of the year John Henson, who sprained his left wrist in last week’s ACC tournament in Atlanta, but cruised past Vermont 77-58. Without Henson, the Tar Heels still got 17 points each from two other big men, Tyler Zeller and Henson’s substitute James Michael McAdoo.

UNC’s Harrison Barnes will face his former Ames (Iowa) High School teammate Doug McDermott of Creighton on Sunday after McDermott used 16 points and a key offensive rebound late to help hold off Alabama 58-57.

The ACC tournament champion Seminoles got all they could handle from the champion of the Atlantic 10 tournament, No. 14-seed St. Bonaventure, trailing for the game’s first 33 minutes. FSU standout guard Michael Snaer picked up two fouls in the first 2 1/2 minutes of the game and never scored, finishing 0-for-7.

The No. 3-seed Seminoles withstood three consecutive 3-pointers late from the Bonnies to avoid losing for the second consecutive year to a mid-major, after falling to VCU in last year’s Sweet 16.

N.C. State won its first NCAA tournament game since defeating California in 2006 under coach Herb Sendek, 79-65 over San Diego State.

First-year coach Mark Gottfried appreciated the contribution from N.C. State’s Atlanta connection Friday as Wheeler graduate Richard Howell scored 22 points in 28 minutes on 10-of-12 shooting, and Roswell’s Lorenzo Brown flirted with a triple-double (17 points, nine rebounds, eight assists).

“We made the decision to go toward Richard, and he lit up like a Christmas tree,” Gottfried said.

Virginia had a forgettable end to its season in a matchup many figured to be a good one. Florida missed its first 13 3-point shots and made only 4-of-23 for the game but still beat the Cavaliers with ease 71-45.

Information from The Associated Press was used in this article.