Moore was in charge of the Millers for 485 games over two spells
Rotherham manager Ronnie Moore and assistant boss Jimmy Mullen have left the club by mutual consent.
The Millers, who were third in League Two at the end of February, have since picked up three points from five games.
They now lie five points adrift of the automatic promotion places after a run of five games without a win, including Saturday's 5-0 defeat at Chesterfield.
Andy Liddell will take caretaker charge until the summer, assisted by Paul Warne, Andy Dibble and Nicky Eaden.
It was Moore's second spell in charge of Rotherham after previously managing the Yorkshire club between 1997 and 2005, leading them to back-to-back promotions from the old Division Three to Division One.
He returned in September 2009
along with former Burnley and Walsall boss Mullen and led the Millers to last season's League Two play-off final where they were beaten 3-2 by Dagenham & Redbridge.
A statement on the Millers website
read: "The club would like to place on record our thanks to Ronnie and Jimmy for their wholehearted contribution to Rotherham United over a number of years in both playing and coaching capacities.
"Both will be warmly received by the club and we wish them well for the future."
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