The 3-2 reverse was the Cod Army's third consecutive defeat in all competitions but they remain well-placed in League Two, where they currently occupy the final play-off spot after 20 matches of their debut Football League season.
Mellon, 40, led Fleetwood to the Blue Square Bet Premier title last season having also masterminded their ascent from the Conference North two years earlier.
A brief statement on the club's official website read: "Fleetwood Town wish to announce that manager Micky Mellon's contract has been terminated with immediate effect.
"The club would like to place on record our sincere appreciation for what he has achieved during his time with the club."
