The Cardinals (16-1, 4-0 Big East) won their 11th straight game and like the others they relied on their star backcourt and pressure defense.
The only other time Louisville was ranked No. 1 in The Associated Press' Top 25 was the final poll of 2008-09. The Cardinals won the national championship in 1980 and 1986 but the AP does not conduct a post-NCAA tournament poll.
The Cardinals are the third team to hold the No. 1 spot this season along with Indiana and Duke and they celebrated the move with the convincing road win.
Louisville shot 60.7 percent in the second half (17 of 28) and hit an even 50 percent for the game.
Omar Calhoun led the Huskies (12-4, 2-2) with 20 points while Shabazz Napier added 12, all but two in the first half. Ryan Boatright had 11 points and he and Napier both had six assists for the Huskies, who were coming off a win over then-No. 17 Notre Dame that was their sixth in seven games.
Louisville's backcourt of Smith and Peyton Siva didn't get to spend much time together on the court. For Siva, it was foul trouble, for Smith it was what appeared to be leg cramps after he played all 20 minutes of the first half.
Siva, the conference preseason Player of the Year, picked up his second foul just 3:47 into the game. Not only did the Cardinals lose a veteran leader when the senior went out but Smith, the leading scorer at 18.7 points per game, had to assume more of a role in running the offense. It didn't hurt his scoring much, though, as he had 15 points on 7-of-13 shooting as Connecticut took a 34-28 halftime lead.
Dieng had two points and 10 rebounds in the first half. He missed all five shots he took but he had four offensive rebounds.
Connecticut scored the first basket of the second half for a 36-28 lead but that's when Louisville started looking like the No. 1 team in the country.
They went on an 8-0 run in which Smith had four points and Siva two. That was part of a 19-5 burst that gave Louisville a 47-41 lead with 12:18 to play.
Connecticut, which shot 53.8 percent from the field in the first half, had just three field goals in the opening 13 minutes of the second half as Louisville went ahead 60-44. The Huskies, who went 9 minutes without a field goal at one stretch, had trouble moving the ball against the fullcourt pressure and 2/3 zone of the Cardinals. The Huskies had seven turnovers in the first 11 minutes of the second half, matching their total in the first half.
Siva picked up his third foul with 14:21 to play in the game and he returned to the bench. When he came back in the game with 10 minutes left, Smith went to the bench for treatment. Siva hit a 3-pointer 50 seconds later as part of the big run. Siva finished with 11 points and four assists.
The Huskies shot 25.9 percent in the second half (7 of 27) and were at 39.6 percent for the game.
Connecticut drops to 2-7 all-time against No. 1 teams with the last win over Texas on Jan. 23, 2010.