Victory came into the game having not won an opening-round fixture since 2006, but emphatically ended that hoodoo with a dominant display at the Etihad Stadium.
New recruits Matthieu Delpierre and Besart Berisha each found the target, together with Leigh Broxham, inside the opening half-hour as the hosts raced into a three-goal lead.
The Wanderers, who take on Al Hilal of Saudi Arabia later this month in a two-legged Champions League final, replied through Mark Bridge before the break but there was to be no way back, with Archie Thompson adding a fourth for Victory early in the second period.
A delighted Berisha, who moved to Melbourne in a high-profile close-season switch from Brisbane Roar, said: "It's always good to win the first game, but what was really important for us was the way we played. From the first minute. I'm very happy with the performance."
"We had a really tough pre-season and we're so happy that everything in the game was how we expected."
Delpierre took just eight minutes to open the scoring with an accomplished volley from Guilherme Finkler's free-kick.
Berisha then converted a penalty following Antony Golec's handball in the area and Broxham fired home a rebound to make it 3-0 after Ante Covic had denied Kosta Barbarouses.
Although Bridge pulled a goal back from Labinot Haliti's hooked ball forward, Victory retained control of proceedings.
Good work from Carl Valeri and Berisha enabled Thompson to restore his side's three-goal cushion in the 54th minute and the Wanderers will know they have plenty of work to do ahead of next weekend's derby against Sydney FC.
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