Ryan McMahon added 12 points and Steven Enoch had 10 for the Cardinals (20-12), who'll face No. 3 North Carolina for the third time this season in the quarterfinals on Thursday night.
The Cardinals blew open a nine-point game in the second half with a 22-7 run to build a 24-point lead.
Louisville's length clearly bothered Notre Dame as the Irish were held to 27 percent shooting from the field and 11 percent from 3-point range.
Louisville also dominated on the glass, outrebounding Notre Dame 50-38.
T.J. Gibbs led the Irish (14-19) with 21 points. The Cardinals held John Mooney, Notre Dame's leading scorer, to seven points on 3-of-18 shooting.
The seventh-seeded Cardinals wasted no time jumping on the 15th-seeded Irish, bolting to a 28-12 lead behind 12 points from Nwora and a rim-rattling put-back dunk from Enoch — one of many dunks from the high-flying Cardinals. Still, Notre Dame cut the lead to nine at halftime despite missing its final 12 3-point shots of the first half.
Nate Laszewski returned to the Notre Dame starting lineup after injuring his back and missing the second half of the Irish's first round win over Georgia Tech, but was held scoreless on 0-for-6 shooting from the field.
BIG PICTURE
Notre Dame: Mike Brey knows this is a rebuilding year for his young team, so he has to be pleased his team won its first round game against Georgia Tech to snap a seven-game skid. The Irish's young core will benefit from another year of experience, but this team needs more size and athleticism to get back to competing at the highest level in the ACC.
Louisville: The Cardinals are looking like a solid lock for the NCAA Tournament. And, this is a team that could continue playing in the ACC Tournament. They beat the Tar Heels by 19 in Chapel Hill, North Carolina in January, although North Carolina avenged that loss with a 79-69 win at Louisville on Feb. 2.
UP NEXT
Notre Dame: Season over.
Louisville: Faces No. 3 North Carolina on Thursday night.