DENVER (AP) — Demonte Harper of 13th-seeded Morehead State dribbled patiently, watching the clock tick down — 10, 9, 8, 7 — then stepped up behind the 3-point line, swished the shot and crumpled Louisville's NCAA hopes, to say nothing of a few million tournament brackets.

Harper's 3-pointer from the top of the circle with 4.2 seconds left Thursday led to the first big upset of the NCAA tournament, a 62-61 win over No. 4 Louisville in the Southwest regional that sent the underdog Eagles (25-9) tumbling to the floor in jubilation.

After Harper's go-ahead basket, the Cardinals (25-10) had a chance to win it, but Morehead's best player, NBA-bound center Kenneth Faried, blocked Mike Marra's attempt from the corner.

The buzzer sounded. Louisville was gone after its first game for the second straight year and tiny Morehead State of Kentucky — enrollment 9,000 at the base of the Appalachian Mountains — had its first tournament win since 1984.

Chris Smith had 17 points for Louisville, which closed the year on its first two-game losing streak of the season. Morehead State will play No. 5 Vanderbilt or No. 12 Richmond.

After Morehead State called timeout for its last possession with 23.8 seconds left, Harper seemed an unlikely candidate to take the most important shot in the program's short, unheralded history. He was 2 for 9 from the floor and hadn't hit any of his five 3-point attempts.

Meanwhile, Morehead State had the big fella, Faried, not to mention Terrance Hill (5 for 6) and Ty Proffitt (3 for 6), each of whom were lighting it up from 3-point range all afternoon.

The Eagles, however, didn't do anything by the book in this one.

If they were going to win, it was supposed to be on the shoulders of Faried, the all-time rebounding leader in Division I. Faried pulled down 17 rebounds but had a terrible day from the field — 4 for 17 for 12 points — and wasn't the biggest factor in this game.

He'll get another chance, though. He can thank Harper — whose only shot of the second half gave him a total of eight points — and Hill, who scored a career-high 23, including 12 during a 16-4 run that turned a seven-point deficit into a 57-52 lead with 5:24 left.

Louisville answered with the next nine points and the upset chances looked all but over with 1:14 left. But the Eagles worked the ball to Faried and he converted two free throws after a foul. Then, Morehead State fouled Elisha Justice, who missed the front end of a 1-and-1. Faried got the rebound, and coach Donnie Tyndall set up the play that would make him a winner.

And as game-winning plays go, this one was quite simple. No picks, no passes.

Harper took the inbounds pass in the backcourt, wasted a few seconds, dribbled across the line and stood there dribbling for a few more seconds. Then he improvised — a little move to the left to create some space against Peyton Siva, then a spot-up jumper that dropped in clean.

Faried punctuated the win with his block on Marra, proving yet again that he doesn't have to have the ball in his hands to impact the game.

The prototypical NCAA celebration ensued — players pounding their chests, snapping their jerseys, sprawling on the floor. Tyndall did a quick interview and walked away — no smile, no shrug, no pointing to the small group of fans who made the trip from Kentucky. Just another scouting report to do and a game on Saturday.

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Not so for Louisville, which overachieved all year long during what Rick Pitino said would be a "bridge season" — not quite a rebuilding year, but not quite one with high expectations.

The Cardinals did better than most people figured, finishing third in the Big East, then making the final of the postseason tournament.

They won with heart and a series of wild comebacks. But they had no single star, no one who could take a game over. And when they fell behind 10-0 early by missing their first nine shots — seven from the field and two from the line — it was clear they'd be in for a big day's work.

It turned out to be more than they could handle. But not too much for Morehead State — a team that wasn't plucky or lucky on this day, but rather, simply good enough to pull off the first upset of the 2011 version of March Madness.