The 51-year-old was relieved of his duties following a 3-1 defeat to Oxford United on Tuesday night.
Fleetwood are currently in the League One relegation zone and are three points from safety - winless in eight.
Grayson had been at the club less than 12 months having come in on an interim basis last January, arriving on the final day of the transfer window.
He settled the ship at Highbury following the tenure of Joey Barton and was rewarded with the role full time.
Former Blackburn Rovers midfielder and assistant head coach David Dunn has also left Fleetwood.
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