The 52-year-old met with Arizona president Dr. Robert Robbins and athletic director Dave Heeke for over an hour late Tuesday, and the decision to break from the coach was made after another meeting Wednesday morning, sources told Jeff Goodman of Stadium.
Arizona said it will honor the remainder of Miller's contract. He had one year left on his deal and is owed $1.5 million, according to Goodman.
"We appreciate Sean's commitment to our basketball program and to the university," Heeke said in a statement. "After taking the many factors involved into account, we simply believe that we need a fresh start and now is the time. I want to thank Sean, Amy, and their sons for their service to the university and wish them the very best in the future."
Associate head coach Jack Murphy will serve as interim head coach.
Miller had been with the Wildcats since 2009. He amassed a combined 302-109 record over 12 seasons in Arizona, complete with seven trips to the NCAA Tournament and three Pac-12 Tournament titles.
However, the head coach has been the subject of heavy scrutiny in recent years and was reportedly being investigated by the FBI in connection with the 2017 NCAA basketball corruption scandal. It was reported in October that Miller and Arizona's basketball program were facing multiple Level I violations from the NCAA, with Miller cited for lack of head coach control.
Arizona is still awaiting its fate in the NCAA's investigation, according to The Associated Press.
Gonzaga assistant coach Tommy Lloyd has been linked to the Wildcats' head coaching role in recent days, according to ESPN's Jeff Borzello.