The Knights announced last week that Brown's time at the helm would come to an end after the 2019 season.
However, the 46-year-old has left effective immediately, the Knights said in a statement on Tuesday.
"The nib Newcastle Knights can confirm coach Nathan Brown has departed the club effective immediately," a statement read.
BREAKING NEWS: Nathan Brown to depart the club, effective immediately.
— Newcastle Knights (@NRLKnights) August 27, 2019
"This decision has been made in conjunction with Brown in the best interest of the club.
"Kristian Woolf will take over as interim coach for the remainder of the 2019 season."
With two games remaining, Newcastle are 11th in the NRL ladder, three points behind eighth-placed Brisbane Broncos.
Photo Getty Images Caption: Former Newcastle Knights coach Nathan Brown