Otto Porter scored 17 points and grabbed 12 rebounds, leading Georgetown to a 53-51 victory over fifth-ranked Louisville at the Verizon Center.
Markel Starks also scored 17 for the Hoyas (14-4, 4-3 Big East), who have won two straight and four of their last five.
Russ Smith, Luke Hancock and Gorgui Dieng each scored 12 for Louisville (16-4, 4-3), which has lost three straight for the first time since 2010. The Cardinals were the top-ranked team in the nation last week, but have since lost to Syracuse, Villanova and now Georgetown.
Peyton Siva failed to score for Louisville, but the senior had a chance to give the Cardinals the victory late. He had the ball in the closing seconds trailing 52-51 and missed a jumper from just inside the arc.
Porter was fouled with 1.4 seconds to play and made the first free throw before missing the second. Without a timeout, Louisville was unable to get more than a three-quarter court heave as time expired.
"We had to overcome a lot of poor shooting from a lot of players, but we did it with defense, we just didn't do it by rebounding," Louisville coach Rick Pitino said. "They won the game by us not blocking out twice when we could have had the lead and that really, really hurt us and that was the difference maker in the game."
Georgetown broke open a tight game early with an 11-2 run. Porter fueled the burst with a three and D'Vauntes Smith-Rivera hit two from the line for a 21-12 lead with 11:09 left in the first half. The Cardinals managed to stay within striking distance and got as close as two before heading to the break down 33-29.
Louisville scored the first five points of the second half and eight of the first 10. Hancock hit consecutive threes to give the Cardinals a 37-35 edge, but Georgetown answered with a 10-2 run and opened a 45-39 advantage on a Starks jumper with just over nine minutes to play.
The Cardinals, though, crept back over the next three-plus minutes and tied it at 48-48 on a Dieng dunk. After a tip-in by Nate Lubick, Dieng's layup again tied the game with 4:14 remaining.
Aaron Bowen's tip-in, his only basket of the game, gave Georgetown a 52-50 lead and Chane Behanan made just one free throw with 2:22 left to keep Louisville down a point.
Porter missed a three with the shot-clock running down and Wayne Blackshear missed from beyond the arc at the other end. The Hoyas, trying to milk the clock, turned it over with just over a minute left and Smith missed a tough shot for Louisville with 34 seconds left, but Porter again turned it over to give Louisville one final chance that ended in Siva's miss.
"We defended together. In the huddle, we told each other we have to stop them and rebound the ball," Porter said.
Porter had seven of Georgetown's 17 turnovers ... Siva, after scoring 15 points and handing out a career-high 13 assists on Tuesday in the loss at Villanova, took just two shots and had only two assists Saturday ... Both teams struggled from the field, as Georgetown made 38.8 percent and Louisville connected on just 34.8 percent. The Cardinals were also only 3-of-11 from three-point range ... The Hoyas lead all-time series, 9-4, and have won the last four meetings ... Louisville last dropped three in a row from Jan. 11-21, 2010.