The former Cardiff boss was in charge of the Addicks for less than six months after joining in the summer.
A club statement read: "The club has reluctantly made this decision after results this season, which have left the team occupying 15th place. The club wants to give itself the best possible opportunity of achieving its number one priority - winning promotion to the Sky Bet Championship at the earliest opportunity.
"The club would like to thank Russell for his tireless work during his time at The Valley, particularly the processes and disciplines he has instilled at the training ground, and wishes him well for the future".
Slade becomes the sixth manager to leave Charlton in the last two years and Addicks fans are thought to be extremely disappointed with the running of the south London club.