McCarthy led the Pack to Super Bowl 45 victory against the Pittsburgh Steelers but the side have struggled this season.
They currently have a 4-7-1 record and are third in the NFC North.
President and chief executive officer Mark Murphy said: “The 2018 season has not lived up to the expectations and standards of the Green Bay Packers.
“As a result, I made the difficult decision to relieve Mike McCarthy of his role as head coach, effective immediately.
“Mike has been a terrific head coach and leader of the Packers for 13 seasons, during which time we experienced a great deal of success on and off the field.”