After an uninspiring first half at Hunter Stadium on Sunday, the Panthers and the Knights were locked at 6-6 at the break.
But Penrith dominated the second stanza, leaving the Knights to extend their club record losing streak to 15 games.
It also puts Newcastle into the top 10 on the all-time longest losing streak list.
The Knights enjoyed 60 per cent of the possession in the first half, but despite repeated opportunities they could not crack the Panthers' line.
Instead, it was the Panthers who opened the scoring, with winger Josh Mansour crossing untouched in the 12th minute after some good lead-up work by Waqa Blake.
The Knights hit back after 30 minutes when Brendan Elliot plucked a Trent Hodkinson bomb out of the air and raced over.
But that was as close as the Knights got as they capitulated in the second half to let the Panthers run in six unanswered tries.
Matt Moylan broke the deadlock in the 44th minute when he ran off a Peter Wallace pass and touched down under the posts.
From there the floodgates opened, with Blake (55th minute) and Tyrone Peachey (59th minute) each beating some flimsy Knights defence to take the score out to 18-6.
Penrith continued to dominate the Knights up the middle of the ruck and made them pay on the edges, with Dallin Watene-Zelezniak scoring a second-half double and Josh Mansour scoring his second as the siren sounded.
The Panthers have now won four out of their past five matches and have leapfrogged the Titans into seventh spot on 26 points.