Pitino is the 38th coach to reach 600 wins. He is the 15th fastest to the milestone, doing it one game quicker than former Louisville coach Denny Crum.
The full-court press that has sparked so many of Pitino's victories was on display early as the Cardinals scored 18 first-half points off 13 turnovers.
Mike Liabo had 15 points and four assists for the Skyhawks.
Louisville never trailed and led 47-23 at the half.
The Cardinals' pressure sparked a five-minute 15-2 run less than four minutes into the game that set the tone for the game and put Louisville up 25-7 with 11:05 left in the first half. The Cardinals forced five of their 21 turnovers during the stretch.
Louisville shared the ball throughout, racking up 20 assists on 31 field goals. The Cardinals were fifth in the NCAA in assists last year with 17.4 a game.
Pitino won a national championship in 1996 at Kentucky and is the only coach to take three different schools (Providence, Kentucky and Louisville) to the Final Four.