Morehead State hadn't beaten Louisville in two previous NCAA Tournament matchups (1984 and 2009).
Meanwhile, Demonte Harper hadn't made a 3-pointer against the Cardinals on March 18, 2011, missing five attempts.
But the third time and Harper's first 3-pointer were the charm for Morehead State.
Down 61-59 to No. 4 seed Louisville, the 13th-seeded Eagles won on Harper's shot with 4.3 seconds remaining.
"The coach said, 'Hey, I dreamed about this last night, this exact situation,'" Harper said. "He said, 'I know exactly who I'm going to. I'm going to put it right in your hands, Demonte.' He said, 'At 6 seconds, I want you to attack and pull up and hit the shot.' I hit the shot. It feels unreal right now."
Kenneth Faried blocked Mike Marra's shot from the corner to clinch the biggest NCAA Tournament victory in Morehead State history, and the sports moment judged the greatest in school history.
"I think to be a first-round game against an in-state power, to be able to knock them off, I don't think it's ever been bigger than that in the history of our school," head coach Donnie Tyndall said.
It was the Eagles’ first win against their in-state rivals since 1956-57. In three previous NCAA Tournament meetings, including the 1961 regional third-place game, Louisville won by an average of 21.7 points.
From 2007-12, it was also the only time a No. 14 seed beat a No. 3 seed in the tournament.
"This is as tough a loss as I've had in coaching," said Louisville's Rick Pitino, "and I've been coaching a long time."
MSU trailed 61-57 with 1:20 left after a Terrance Jennings’ dunk. But moments later, Jennings fouled Faried, who made both free throws to cut Louisville's lead to 61-59.
Harper fouled Elisha Justice immediately, but Justice missed the first of a one-and-one. Faried grabbed the rebound to set up Harper's 3-pointer from the top of the key over Peyton Siva.
Terrance Hill scored a career-high 23 points for the Eagles and Ty Proffitt added 13. Faried recorded his 85th career double-double with 12 points and 17 rebounds.
The two-time Ohio Valley Conference Player of the Year had declared for the 2010 NBA Draft but elected to return for his senior year. He broke Tim Duncan's modern-era (post-1973) Division I career rebounding record of 1,570 rebounds that had stood since 1997.
"Words can't explain how proud I am of my teammates because everybody thinks, 'Morehead State and Kenneth Faried,'" said Faried, who was selected No. 22 overall by the Denver Nuggets in the 2011 NBA Draft.
"But it's Morehead State, 'The Team.' It just speaks volumes about my teammates who just stepped up."
• Morehead State Hall of Fame
On the cover and above: Demonte Harper hits his only 3-pointer of the game to give Morehead State a 62-61 victory against Louisville in the first round of the NCAA Tournament on March 17, 2011, at Pepsi Center in Denver. (Photo by Justin Edmonds/Getty Images)
THIS WEEK’S GREATEST MOMENTS
• Monday: Middle Tennessee and Milwaukee
• Tuesday: Minnesota Duluth and Minnesota State
• Wednesday: Missouri-Kansas City and Morehead State
• Thursday: Murray State and Navy
• Friday: Nebraska Omaha and New Hampshire