Buckles injured the knee in the first half Sunday of the Cardinals' 62-59 victory over Pittsburgh (No. 6 ESPN/USA Today, No. 4 AP). Pitino initially said after the game that the injury was a sprain, but further evaluation revealed the season-ending tear. He will have surgery some time in the next two weeks.
Buckles, Louisville's most versatile frontcourt player, had previously missed 13 games with a badly broken finger.
"I'm really, really disappointed for Rak," Pitino said. "He waited patiently to come back, and now he gets hurt again. I feel absolutely awful for him and the team.
"But we've battled adversity all season and we'll continue to do so, and we won't let it bother us."
Louisville has perhaps been the most injury-riddled team in the country. The Cardinals have had 10 players miss at least one game, and only two have played all 29 games.
Buckles has had flashes of brilliance for Louisville. He produced 20 points and nine rebounds in the last game of his freshman season, an NCAA tournament loss to California. In the first game of this season he had 17 points and 11 rebounds against Butler. For the year the 6-foot-7 Miamian averaged 7.2 points and 6.5 rebounds while providing the Cardinals with their most athletic big man.
Pat Forde is a senior writer for ESPN.com. Information from The Associated Press contributed to this report.