The announcement comes shortly after club head coach Abdeslam Ouaddou had refuted reports of rift between himself and Ncikazi at the press conference ahead of Friday's CAF Champions League second-leg preliminary round clash against African Stars.
According to the statement on the club's website, the decision comes following talks with management on Thursday morning where the former Maritzburg United and Golden Arrows coach revealed his desire to lead another PSL team.
"Mandla leaves with our gratitude and our blessing," read chairman Dr Irvin Khoza's statement.
"His contribution to Orlando Pirates has been evident throughout his time with us. We respect his wish to pursue this new opportunity and wish him success as he takes on a new responsibility."
Ncikazi won nine trophies as part of the Buccaneers technical team serving under coaches Josef Zinnbauer, Jose Riveiro and Ouaddou.
It is unclear which new club the 57-year-old will be coaching after former club Golden Arrows dismissed rumours of a reunion.
Orlando Pirates will be looking to progress to the CAF Champions League group phase when they face African Stars in their second leg clash at Orlando Amstel Arena on Friday.
Mamelodi Sundowns coach Miguel Cardoso believes his side must be prepared to fight for victory when they battle Wiliete SC in their second leg fixture at Loftus Versfeld on Friday.
Golden Arrows have moved to clarify speculation linking Orlando Pirates assistant coach Mandla Ncikazi with a return to the club, insisting that Pitso Dladla remains in charge.
Stellenbosch coach Gavin Hunt has expressed his desire to help veteran striker Bradley Grobler to break the all-time Premier Soccer League top goal scorer record.
