The 63-year-old boss guided Hartlepool to an incredible escape from relegation last season, having taken charge with the club bottom of the Football League standings and six points adrift of safety.
However, the North East side have won just one of their last 10 games this term and are just a place above the drop zone, albeit four points clear, following Tuesday's 2-1 home defeat to Stevenage.
A statement on the club's official website read: "Hartlepool United can announce that manager Ronnie Moore has left the club by mutual consent."
Chairman Gary Coxall added: "This is an extremely difficult decision but one we feel is right for the football club.
"Ronnie has worked tirelessly to bring success to the club during his time at The Vic and we thank him sincerely for those efforts and wish him well for the future."
Moore arrived at Victoria Park in December 2014, and the club won nine and drew six of their final 26 games last season, eventually finishing in 22nd place, four points clear of the drop.