A 2-0 defeat at home to lowly Waasland-Beveren on Sunday proved to be the final straw, with that reverse marking an eighth loss in Genk's last 10 league games.
That result left the 2011 title winners in sixth position, and they are in danger of slipping out of the play-off spots that decide the Belgian champions.
A statement on the club's website read: "After the defeat at home to Waasland-Beveren on Sunday evening it was clear that the much needed turnaround in the results of the Jupiler Pro League has been absent for too long.
"Genk wishes to thank Mario Been for the many successes. An appointment of a new coach will be made as soon as possible."
The former Feyenoord boss took the reins at Genk in August 2011, and led the club to a Belgian Cup triumph last season.
Assistant managers Pierre Denier and Hans Visser will take temporary charge, starting with the club's second-leg encounter at home to Anzhi Makhachkala in the UEFA Europa League on Thursday, with the tie currently locked at 0-0.
