In what is traditionally a clash between title rivals, the contest at Juventus Stadium highlighted the current gulf between the two sides, as Massimiliano Allegri completed a league double over his former employers in a dominant display.
The reigning champions, who are now 39 unbeaten at home in the league, edged ahead in the 14th minute through Carlos Tevez, despite the Argentina international appearing to be offside.
Luca Antonelli, one of two Milan debutants alongside Gabriel Paletta, restored parity just before the half-hour mark, though they were level for only a few minutes, with Leonardo Bonucci restoring Juve's lead.
Milan produced a slight improvement after the break, though Juve also took things up a notch and opened up a two-goal deficit with 25 minutes to go through Alvaro Morata, who finally appears to have dislodged fellow Spaniard Fernando Llorente.
Filippo Inzaghi, who reportedly endured a fractious relationship with Allegri in their time together at Milan, saw his side's late efforts count for nothing, while Juve moved well clear of second-placed Roma ahead of their trip to Calgiari on Sunday.
Juve began the contest in purposeful fashion, pushing forward in numbers and pressing fiercely in midfield, forcing early errors from Milan.
And it came as little surprise when the hosts broke the deadlock 14 minutes in, as Tevez, who looked to have strayed marginally beyond the last defender, latched on to Morata's header and tucked an effort under Diego Lopez after charging away from the helpless Paletta.
The home side crafted another opportunity a few moments later, as Patrice Evra knocked Andrea Pirlo's free-kick delivery back across goal, but nobody could capitalise.
And Milan made the most of that let-off, drawing level with 28 minutes on the clock thanks to Antonelli's fine glancing header.
The visitors were level for barely three minutes, though, as Bonucci stabbed home after Tevez headed Pirlo's corner back into the danger area.
Milan's chances suffered a further blow eight minutes before the break, with top-scorer Jeremy Menez forced off and replaced by Giampaolo Pazzini.
Juve continued to dictate proceedings in the second half, though Milan spurned a good opportunity to equalise for a second time in the 54th minute, Gianluigi Buffon producing a smart save to deny Pazzini.
The hosts swiftly came to grips with Milan's brief improvement and effectively secured all three points in the 65th minute, as Morata was left with an easy tap-in after a Claudio Marchisio effort came back off the post.
Milan's attempts to force an unlikely late comeback left the visitors vulnerable on the break, but Juventus were unable to punish Inzaghi's men further, with Lopez doing well to deny Marchisio with eight minutes left.
In Saturday's other Serie A game, UEFA Europa League hopefuls Torino ran out 3-1 winners at Verona, as efforts from Josef Martinez, Fabio Quagliarella and Omar El Kaddouri eclipsed Luca Toni's goal.
