Edgar Sosa scored 18 points, Jerry Smith added 12 and the Cardinals locked up the Golden Eagles again, winning 71-57 Monday night to snap No. 16 Marquette's 14-game home winning streak.
The Golden Eagles (16-5, 6-4) shot 32 percent from the field. In their previous matchup last month, Louisville dominated 71-51 in Freedom Hall by holding Marquette to 30.4 percent shooting.
Already the last team to beat Marquette in the Bradley Center, Louisville (17-6, 7-3 Big East) didn't have nearly as tough a time as last year when Smith, from the Milwaukee suburb of Wauwatosa, made a 3-pointer at the buzzer for a two-point victory.
On Monday night, the Cardinals looked well rested after their easiest win in their short Big East history, 87-50 over Rutgers on Saturday, and jumped all over their former Conference USA rival from the start.
Marquette came in with a three-game winning streak that including its first conference road win of the season at Cincinnati on Saturday. But it trailed by nine early and never made a run, stifled by its inability to make shots.
After Marquette scored twice early to start the second half, Smith answered, knocking down back-to-back 3s to make it 40-28.
Moments later, Lazar Hayward, leading Marquette with 13.7 points and 6.3 rebounds per game, picked up his fourth foul with 13:58 to play and took a seat as the Golden Eagles never cut the lead back to single digits.
Hayward finished with 2-of-10 from the field with five points and five rebounds. Wesley Matthews had 15 points, and Jerel McNeal finished with 11.
The Cardinals have dominated the series recently, winning six of the last seven matchups, including the last three in Milwaukee.
They were hot from the field in this one, too, shooting 51.1 percent.
Sosa hit a pair of early 3-pointers and Earl Clark, who finished with 11 points, had a thunderous dunk to give Louisville a 19-10 lead.
Marquette point guard Dominic James came off the bench against the Cardinals after starting 85 consecutive games. He finished with eight points and has failed to score in double digits in five of the last six games as he continues to struggle to recover from a sprained right wrist after a hard foul on Jan. 8 against Seton Hall.