Offensive coordinator Jedd Fisch will serve as interim head coach for the remainder of the season. Fisch declined to comment on the move, which was announced by athletic director Dan Guerrero on Sunday -- Mora's 56th birthday.
UCLA fell 28-23 at USC on Saturday night to drop to 5-6.
"Making a coaching change is never easy, but it's an especially difficult decision when you know that a coach has given his all to our University," Guerrero said in a statement. "Jim helped reestablish our football program, and was instrumental in so many ways in moving the program forward.
"While his first four seasons at UCLA were very successful, the past two seasons have not met expectations. We thank Jim and his family for his service to our school and his unquestionable commitment to our student-athletes."
Mora said in a statement later Sunday that he wanted to thank Guerrero and the administration "for giving me the chance to work at a great institution for the past six years. Coaching student-athletes at UCLA has been the most rewarding experience of my career, and I know the future is bright for the program."
He thanked the "outstanding coaches" for their efforts, and the student-athletes he'd had "the privilege to work with."
"Again, thank you for the opportunity to be the head football coach at UCLA. It has truly been an honor."
Mora compiled a 46-30 record with the Bruins, but after going 29-11 in his first three seasons, UCLA is just 17-19. It can still qualify for a bowl game with a win against Cal at the Rose Bowl on Friday, and would accept an invitation pending any conflicts with the school's finals' schedule, a school spokesperson confirmed.
Fisch declined comment on Mora's dismissal, but said he would address the media on Monday. He told ESPN his focus was on "trying to game plan for Cal."
Guerrero will lead the search for Mora's replacement and be assisted by senior associate athletic director Josh Rebholz, booster Casey Wasserman and former UCLA quarterback Troy Aikman.
Under the terms of his contract, Mora is owed approximately $12.36 million. UCLA said it will exclusively use department-generated funds to cover the cost. Before bonuses, he was scheduled to make roughly $3.7 million annually through the 2021 season. He was California's highest-paid state employee.
As it became clear UCLA would fail to meet expectations for a consecutive season, Mora addressed his job status last week.
"Every day that I've ever coached football, I've felt like I'm coaching for my job, so nothing's ever changed," he said. "Every day, I'm going to go into the office and I'm going to do the best I can, and I'm not going to leave until I've done everything I can to be the best I can be."
The Bruins won 13 of their first 20 games against ranked teams in Mora's tenure, but have since lost six straight. They also won three straight against rival USC after Mora was hired, and have now lost three in a row.
UCLA currently has the nation's No. 14-ranked recruiting class for 2018 and has finished with a top-20 class the past three years.