Popovic, 47, took over at Perth in mid-2018 and helped the A-League club win the premiership in his first season.
But after two seasons at the helm, the former Australia and Crystal Palace defender is leaving, with reports suggesting he will become coach of second-tier Greek club Xanthi.
"I'd just like to thank the players, staff, members and fans and everyone involved with the club, as well as the owner, Tony Sage, for giving me the opportunity," Popovic said via a statement. "I had a wonderful two years, winning the Premiers' Plate being a fantastic highlight, along with playing in front of a sell-out crowd at Optus Stadium in the Grand Final and being a part of the club's first foray into the AFC Champions League.
"Then in our second season, coming through a difficult COVID situation and being one game away from another Grand Final.
"I've really enjoyed my time in Perth, working with great people and living in the city. An opportunity has now come for me to pursue in Europe, but I'm very thankful to everyone for making my time in Perth so enjoyable.
"I wish the club all the very best and it is definitely in good hands. There are wonderful players in the squad and it's been a great pleasure to watch them perform and grow both as players and as young men during my time there.
"The template has been set for Glory being a consistently successful club having challenged for honours in two consecutive seasons and I'm sure the players and staff can now build on that and maintain that consistency in years to come."
Popovic's move is set to be his second stint in Europe as coach, having lasted just nine games in charge of Turkish club Karabukspor in 2017.
Xanthi was relegated from the Greek Super League last season.