Keatts will take over the Seahawks' program after the Cardinals finish play in the NCAA tournament. Louisville faces Kentucky in the Sweet 16 on Friday.
UNCW finished 9-23 this season under fourth-year coach Buzz Peterson, including 3-13 in the Colonial Athletic Association. Peterson was fired earlier this month, after having gone 42-80 with the Seahawks.
"Kevin Keatts is one of the top young basketball coaches in the country and we welcome him to the Seahawk family," UNCW athletic director Jimmy Bass said in a release. "We're very excited about what lies ahead for our program."
The 41-year-old Keatts is in his third season on Rick Pitino's staff at Louisville. He coached previously at Hargrave Military Academy in Chatham, Va.
"I am looking forward to helping restore the men's basketball program and get it back where it needs to be in order to be successful," Keatts said in a release. "I will bring an up-tempo style of play to UNCW that players will want to play in, fans will want to watch."
Pitino already has 11 former assistants serving as college head coaches, including five who advanced to the NCAA tournament.
"Kevin has been one of the best assistant coaches with which I have had the good fortune to work, and I've had a lot of them," Pitino said in the UNCW release. "He is a terrific person, coach, scout, family man and recruiter. He possesses all of the variables to build a successful program. We are really going to miss his upbeat personality that provided sunshine to each of us daily."