Francisco Garcia scored 12 points for the Cardinals (21-4, 9-2 Conference USA), who went 5-for-15 from 3-point range and were 20-of-54 overall (37 percent).
Terrence Leather scored 18 points to lead South Florida (10-12, 3-8), which lost for the eighth time in 10 games.
The Cardinals shot a season-low 33 percent in an 85-68 loss to Memphis on Wednesday and looked just as out of sync against the Bulls.
South Florida jumped to a 14-4 lead as Garcia, Dean and O'Bannon - Louisville's top three scorers - failed to score in the first 10 minutes. O'Bannon missed an uncontested two-handed dunk and Dean banged a short jumper off the bottom of the backboard during the dry spell.
Louisville's defense triggered a 14-2 run, forcing six turnovers in a 5-minute span. O'Bannon's layup with 8:11 left in the first half gave the Cardinals their first lead, 18-16.
But the Cardinals couldn't shake the Bulls, leading only 27-24 at halftime after going 1-for-7 from 3-point range and 9-for-27 overall in the opening 20 minutes.
Coach Rick Pitino kept his team on the bench during a halftime ceremony honoring Louisville's 1980 NCAA championship squad. Former coach Denny Crum, leading scorer Darrell Griffith and the rest of that team shook hands with the current Cardinals before filing off the floor to a standing ovation.
Garcia hit his first 3-pointer with 14:17 left to start a 13-4 Louisville spurt. Dean's 3-pointer 3 minutes later finished the run, but the Cardinals then went 4 minutes without a point.
Marlyn Bryant converted a three-point play with 9:45 left during an 8-0 Bulls' run that cut Louisville's lead to 47-42.
But the Bulls were also plagued by bad shooting and never got closer. They went 3 minutes without a field goal as the Cardinals gradually pushed the lead back into double digits.
Bryant hit a 3-pointer with 1:04 left to end the Bulls' drought, but the basket only cut Louisville's lead to 63-54.
South Florida shot 10-of-29 in the second half (34.5 percent) and finished 20-of-51 (39 percent).
The Cardinals were averaging more than 85 points per game, fifth in the nation, but failed to reach 70 points in consecutive games for the first time this season.