The Cardinals simply used a tight zone defense most of the game to take away the inside scoring of Kentucky's Chuck Hayes and Erik Daniels.
They also made sure they kept close contact with Gerald Fitch, UK's leading scorer and best 3-point shooter.
Louisville also made sure it did not allow Kentucky to consistently ignite its fast break.
The result was a Kentucky offense that looked in disarray in the second half when Louisville, just as it did last year for Pitino, came back to beat the Wildcats.
"I'm stunned," Pitino, the former Kentucky coach, said after the victory, which he called his best "moment" as a coach.
Pitino compared UK's Hayes and Daniels to former UCLA greats Sidney Wicks and Curtis Rowe, two undersized interior players who led the Bruins to championship years before Daniels and Hayes were born. He also said he still believes that both Wildcats will eventually play in the NBA.
But on Saturday the Cardinals limited the UK duo to 6-for-19 shooting from the field and seldom gave them the easy inside shots they had made in the Wildcats' seven previous games.
They also cut off passing lanes for either player to find open teammates, one reason Hayes and Daniels offset a combined four assists with four turnovers.
"We played great post defense," Pitino said. "We told our players if we got to them while the ball was still in the air, we could trap them. If we got there after they received it, they would find the open man. But we did a great job on both of them."
The Cardinals did. But Kentucky also helped with ineffective offense of its own. Players missed open shots. Players became hesitant to take shots. Players made bad passes.
Kentucky coach Tubby Smith said that point guard Cliff Hawkins "disappeared" in the second half, when he had five turnovers, two assists and no points in 10 minutes of play after scoring 12 points in the first half, when he was 4-for-6 from 3-point range.
Fitch hit a big shot to cut Louisville's lead to 57-55 with 95 seconds to play, but he was just 3-for-12 from the field.
"If they are taking away the inside, you've got to be ready to shoot on the outside," Smith said. "I don't know what our guys were thinking."
Of course, the Cats did put up 25 3-pointers to just 14 by the Cardinals. It's just that UK seemed to force most of its outside shots rather than wait for open looks.
The Wildcats also gave Hayes and Daniels almost no help on the boards. After holding an early 11-5 rebounding advantage, UK was outrebounded 38-30 for the game. That was the first time this season it had been outrebounded. Hayes and Daniels had 17 of UK's rebounds.
Still, the most disappointing part of the game for Smith was Kentucky's lack of poise in the second half. Hawkins picked up his third foul early in the second half for throwing an elbow while he was being guarded, and also got his fourth foul on a foolish play.
"It just seemed once again that we did not play with poise and patience," Smith said.
That's supposed to be UK's strength. The Wildcats start three seniors and a junior. They are supposed to be able to play well under pressure, not wilt like they did Saturday.
Louisville sophomores Francisco Garcia and Taquan Dean both failed to score in the first half and were challenged by Pitino to find other ways to help the Cardinals win. Both hit big 3-point shots late in the game and combined for 15 points in the second half.
Kentucky's older players didn't respond nearly as well to a halftime plea from their coach to rebound better and stop Louisville from getting inside with the basketball.
"That (a lack of poise) is what is so bothersome," Smith said.
The Wildcats know they face a painful film session with Smith today. "The film won't lie," Smith said.
He wants his players to see that they must make more of a commitment to winning than they have and that being ranked No. 1 so early in the season meant nothing. Obviously, Louisville already knew that, because it beat then-No. 1 Forida earlier this season before stunning Kentucky.
The Wildcats looked even worse last year when they lost to the Cardinals. This game was more about what Louisville did well and how it earned the win. However, even after last year's loss, Kentucky did come back to win 26 straight games.
Can that happen again?
"I sometimes think Kentucky fans would rather beat Louisville than win the national championship," Hayes said. "But we can't think that way. This game hurts. But we can come back, just like we did last year. It's not what we wanted, but now that's all we can do."