The clash of the co-competition leaders had been billed as the match of the season but Melbourne lost Kiwis halfback Jahrome Hughes before kick off with a calf injury.
With star fullback Ryan Papenhuyzen and strike centre Reimis Smith already out their attack was stifled.
Rookies Cooper Johns and Tyran Wishart were called up to replace Hughes and Papenhuyzen, but the sons of former Kangaroos, Matt Johns and Rod Wishart, had a tough night as Penrith roared to their ninth win of the season.