Macarthur said they and Yorke had reached an agreement to terminate the remainder of his contract, allowing him to "pursue other opportunities".
The former Manchester United, Aston Villa and Trinidad and Tobago forward was appointed Macarthur boss last summer on a two-year deal, his first managerial role, and oversaw them winning the Australia Cup in October.
Yorke told Macarthur's official website: "I want to thank the chairman Gino Marra, CEO Sam Krslovic, all the ownership group as well as all the staff and fans of Macarthur FC.
"I leave the football club with a great team that will continue to challenge for more silverware"
Yorke's assistant, Russell Latapy, has also agreed to leave the club as part of the agreement.
Marra said: "I would like to thank Dwight Yorke and his assistant Russell Latapy for their contribution towards our club and, in particular, Dwight leading Macarthur to our first silverware with our 2022 Australia Cup triumph."
Macarthur are currently sixth in the 2022-23 A-League table with 17 points from 13 games.