Zdrilic, who had been starting the second campaign in a three-year contract, was shown the door after his side crashed to a 4-0 defeat at the hands of champions Melbourne City last weekend.
They had drawn their opening fixture, 2-2 with Wellington, and lie bottom of the early A-League table.
Glory players were informed of the decision by Anthony Radlich, the club's chief executive, on Tuesday night. The club then issued a statement saying the former Socceroos striker had been "relieved of his duties with immediate effect".
The statement continued: "Owner and chairman Ross Pelligra and the Perth Glory board would like to place on record their gratitude to David for his hard work and professionalism throughout his tenure at the club and wish him every success in his future endeavours.
"Members of the existing support staff will take temporary charge of the team for Friday's home game against Melbourne Victory, and an announcement regarding the appointment of a new, permanent head coach will be made in due course."
Glory's poor start follows a dismal 2024-25 season in which they collected just 17 points from 26 games and conceded a league-high 56 goals. They managed just four wins and suffered 17 defeats.
It was the 51-year old's first head coach job, having moved from an assistant's position at home-town Sydney FC in July 2024. He had previous coaching roles in Germany, the United States and Italy.
John Aloisi, an A-League championship-winning coach in 2022 with the currently inactive Western United, is an early front-runner to fill the Glory vacancy.
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