"It is frustrating," said Pitino, recalling that he's been on the other side of some lopsided scores in his career.
"There's not much you can do because the subs I'm putting in the game on our basketball team, with the exception of maybe the top two guys, are just as good as the guys on the court."
Taquan Dean scored 16 points and Francisco Garcia had 15 to pace a balanced attack and lead Louisville (11-1, 2-0) to its 11th straight victory. The Cardinals have won their first two conference games by an average of 39.5 points and haven't lost since dropping their season opener by one point to Iowa in overtime.
"Louisville is an outstanding team. We knew that," said Robert McCullum, South Florida's first-year coach.
"Not only are they an outstanding team, but they're playing extremely well. Often times, you run into a team, and although they're very talented and deep and have all of the ingredients that Louisville has, they might not be playing particularly well at that time."
South Florida (6-6, 0-1) played without guard Marlyn Bryant, who suffered a season-ending knee injury in practice this week, and narrowly missed setting school records for largest margin of defeat and fewest points in a game.
The Bulls shot just 26.5 percent from the field and turned the ball over 22 times. Jimmy Baxter's 3-pointer in the final minute ensured his team would finish with more than the 36 points South Florida scored in a 35-point loss to Marquette in February 1997.
"I think we played as bad basketball as I've seen at South Florida," said Baxter, a senior. "Coach McCullum couldn't have prepared us any better than he did for this, and we just flat out laid down."
Pitino said Louisville simply had too much firepower.
"The worst type of team to play when you're shorthanded is a team that plays 11 people and is deep and presses. So we weren't the ideal opponent for a team that has injuries and is banged up," Pitino said. "Nevertheless, our guys played great defense."
Rick Pitino shakes hands with Francisco Garcia as he is taken out of their game with South Florida.
Louisville held Southern Mississippi scoreless for nearly 13 minutes during a 34-point blowout in its C-USA opener. The Cardinals were just as impressive this time, forcing 15 turnovers in the first half and using an 18-0 run over a 7-minute stretch to build a 20-point lead.
South Florida, playing its conference opener after an 11-day layoff, missed 15 of it first 20 shots and trailed 40-15 before Louisville began the second half with a 20-4 run that put the Cardinals up 60-19 with just under 16 minutes to go.
The Bulls lost to Syracuse by 46 points in December 1987. Bradley Mosley's free throws in the closing seconds enabled South Florida to avoid that mark.
Mosley led South Florida with eight points on 2-for-10 shooting. Baxter and Brian Swift each scored seven.
Louisville shot 51 percent (31-for-61) and made 10 3-pointers. Dean and O'Bannon were both 4-for-5 from behind the arc.
"It's just one game in the conference. We can't hang our hats on one game," Baxter said. "We've got more Conference USA teams coming up. If we hang our hats on this one game, we might as well go back and play high school basketball."