Kevin Muscat's men brushed aside their local rivals, who were forced to play the majority of the match a man down following an early dismissal
A 20th-minute red card to Heart defender Patrick Kisnorbo changed the game before Mitch Nichols netted a brace and James Troisi also scored, while Nick Kalmar claimed a consolation goal late on for John Aloisi's men.
The loss is sure to increase the pressure on Heart coach Aloisi despite the circumstances, with his team yet to win in 11 games this season and sitting last.
They are without a win in their past 16 matches since February, while the Victory jump to third on the ladder.
The Heart were the livelier team early on, largely thanks to the influence of captain Harry Kewell.
Malta international Michael Mifsud had the first shot on target after Pablo Contreras' error, but Nathan Coe saved comfortably on 12 minutes.
Despite the Heart's promising start, the game turned in the Victory's favour on 20 minutes.
Connor Pain's threatening run at the Heart defence led to Kisnorbo's reckless, studs-up challenge and Ben Williams had no hesitation in showing the defender a red card.
Andrew Redmayne was forced into a smart save from Kosta Barbarouses before his error led to the opener on 38 minutes.
His dreadful low clearance fell for Mark Milligan, whose first-time pass found Nichols - kept onside by Patrick Gerhardt - to place past Redmayne.
Milligan headed over as the Victory pushed for a second while Pain hit the post and then blazed a good opportunity over the bar.
Harry Kewell went close to an equaliser early in the second half as his low strike from inside the area whistled past Coe's left post.
The Victory finally took advantage of their numerical advantage for a second time on the hour-mark as Troisi struck his seventh goal of the campaign to go top of the A-League scoring charts.
He found space between the lines to feed Nichols out right and the former Brisbane attacker returned a pass, allowing Troisi to finish neatly into the bottom corner.
Just three minutes later and the points were sealed as Nichols completed his brace.
Substitute Gui Finkler had an immediate impact after coming on, playing a one-two with Nichols, who poked past Redmayne.
Kalmar missed a decent chance before scoring a consolation goal when Coe's punched clearance hit him in the face and trickled in.
Nichols almost had a hat-trick but saw his long-range effort clip the top of the crossbar as the Victory, who almost added another when Barbarouses slid a shot wide, claimed their second straight win.
Melbourne Heart 1 (Nick Kalmar 80)
Melbourne Victory 3 (Mitch Nichols 38, 63, James Troisi 60)
Crowd: 26,491 @ AAMI Park