Erik Brown shot 8-of-8 from the floor and scored a career-high 22 points as Louisville extended its winning streak to 14 games Wednesday night with a 94-65 victory over the Golden Eagles.
Brown was 5-for-5 from behind the 3-point line, and Louisville (15-1, 6-0 Conference USA) shot 52 percent from the field.
The Cardinals outscored Southern Mississippi (9-8, 2-4) 31-7 in the first 10 minutes of the second half after leading 43-35 at the break.
"All of our guys can shoot the ball well," said Pitino, whose team has won three straight in Hattiesburg. "That run at the end of the first half helped us in the second. After we hit a few shots, it was just like a shark feeding."
Louisville has the second-longest current winning streak in the nation. Oklahoma State pushed its run to 15 games Wednesday.
The Cardinals led by eight in the first half before the Golden Eagles trimmed it to 38-35 on two free throws by Jason Forte with 51 seconds left.
Brown hit a 3-pointer and Marvin Stone got a basket in the final minute to push the lead back up.
The Cardinals pushed the lead to 78-48 with 7:16 left on Stone's short jumper. Stone finished with 16 points and 11 rebounds.
"We didn't come out in the second half and play the first five minutes the way that we needed to," Southern Miss coach James Green said. "Louisville is not where it is because of fluke reasons. They are there because they have a lot of talent. They have size and they have shooters."
Reece Gaines had 16 points and 11 assists for Louisville.
Southern Miss has lost four straight. The Golden Eagles shot just 39.3 percent in the second half.
Charles Gaines led Southern Mississippi with 15 points and 13 rebounds. Greg Johnson added 13.