The victory gave Cameron Smith 238 wins, the most of any player in Australian rugby league history.
The first half was among the best played this season.
The Storm started in near perfect fashion. They completed their first 14 sets before spilling their first ball late in the first period. By that stage that had rushed to a 10-0 lead, as they attacked Penrith's left defensive edge.
Suliasi Vunivalu scored Melbourne's opening try after eight minutes after centre Will Chambers created enough space to get on the outside of opposite Tyrone Peachey before delivering the final pass for the giant winger.
The Storm's superstar trio in Smith, Billy Slater and Cooper Cronk combined for the Storm's next try, with Slater playing as the link man in the middle of the field between the two.
A Cronk pass created the overlap needed for Chambers to score to have the Storm leading by 10 after 20 minutes.
Penrith found their rhythm in the second part of the first half. Halves Nathan Cleary and Te Maire Martin linked on one side of the field before some slick footwork by Martin allowed him to slice through the Storm defence.
Melbourne led 10-6 at halftime but took barley a minute to extend their lead in the second half.
A Dale Finucane off-load set up Cronk to extend Melbourne's lead by 10.
Penrith had a chance to fight back minutes later only for interchange prop Moses Leota to spill the ball over the try line as a desperate Smith came in over the top to stop the try.
Despite scoring first in the second half, it was Penrith who dominated territory and possession for the bulk of the second half.
The video referee denied winger Dean Whare a try while half Martin spilt the ball as he attempted to score as the Storm defence held strong.
From the scrum following Martin's error, winger Josh Addo-Carr completed another runaway try to ensure victory for the Storm before Vunivalu had his second on fulltime.
Melbourne Storm 28 (Vunivalu 2, Chambers, Cronk, Addo-Carr tries; Smith 3 goals) def. Penrith Panthers 6 (Martin try, Cleary goal) at AAMI Park.