The Eels opened the scoring through Erick Aukofolau after some quick passes along the left edge, with Mitch Brasington adding the extras in the first of his two successful conversions in the half.
The Knights then returned fire with Honeti Tuha making a break and running 80 metres to score, with David Oakes converting the try.
Not long after and Eels prop Will Bugden crashed over the try line to make the score 12-6 with just over 20 minutes to go.
Knock-ons and silly penalties were the theme of the bulk of the first half, with possession changing hands before a set could be completed for almost ten minutes, before the Knights broke through the line to score through Sione Mata'utia.
The scores looked to be locked up at 12-12 going into the half, but Knights forward Jah Pakau had other ideas, barging through the Parramatta defence on the half-time siren to put the home side ahead 18-12.
The Knights burst out of the blocks in the second half, with Honeti Tuha scoring a quick double, closely followed by Sione Mata'utia scoring his second - all three coming off cross-field kicks being picked up near the posts.
The Eels remained competitive with Zach Dockar-Clay scoring for the Eels with less than 10 minutes remaining - but the Knights weren't finished yet.
Two late tries to Eddie Proudler and David Oakes saw the Knights out of reach, finishing up 46-18 victors.
Newcastle Knights 46 (Tuha 3, Mata'utia 2, Proudler, Oakes, Pakau tries, Oakes 7 goals)
Parramatta Eels 18 (Aukofolau, Dockar-Clay, Bugden tries, Brasington 3 goals)