The fourth-seeded Cardinals (31-5) shot under 45 percent, had 19 turnovers and only got 11 points from star Russ Smith. It didn't matter with the fifth-seeded Billikens (27-7) going 0 for 15 from 3-point range and struggling to take care of the basketball.
Louisville moves on the Midwest Regional semifinals in Indianapolis against either No. 1 seed Wichita State or No. 8 seed Kentucky. The unbeaten Shockers and Wildcats meet Sunday in St. Louis.
Saint Louis, which has never been to the Sweet 16, lost in the third round of the tournament for the third consecutive year. Dwayne Evans led the Billikens with 16 points and Atlantic 10 player of the year Jordair Jett finished with 15.