The Roar finished second-last despite going unbeaten in the final four games of the A-League Men season, including notching three wins.
Zadkovich has been moved on after 38 league games - and just eight wins - at the helm (10 draws, 20 losses) after initially joining as an interim coach last year.
"The club would like to acknowledge and thank Ruben for his commitment and efforts during his tenure in Brisbane," Roar CEO Kaz Patafta said in a statement on Tuesday.
"Ruben leaves with our best wishes for his future endeavours, as we begin to chart a new course here at the club."
In their statement, Brisbane flagged a new coach and said their staff would be appointed "in the coming days".
The Roar will hope their next appointment is able to stick around.
Since Warren Moon's departure in February 2023, caretaker Nick Green, Ross Aloisi, caretaker Luciano Trani, Ben Cahn and Zadkovich have all taken the reins then departed for various reasons.
Brisbane have struggled for relevance for years, with the club seemingly a shadow of the powerhouse that captivated the league with Ange Postecoglou's "Roarcelona" team.
Ross Aloisi took Brisbane to the Australia Cup final in 2023, but the Roar last appeared a genuine threat for ALM silverware when John Aloisi was at the helm between 2015 and 2018.
Former Perth Glory boss Zadkovich will also have to plot his next move in coaching after another difficult spell in a top job.
"I wish to take this opportunity to thank the members and fans at Brisbane Roar, alongside Kaz Patafta and Zac Anderson, for the opportunity to coach at this great club," he said in a statement.
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