Playing in front of a vocal crowd of 23,392, the Knights lead from the start and never looked like taking their feet off the pedal.
The Knights were strong early, with Tyrone Roberts scoring a try and converting it in the first 6 minutes to put the Knights in front.
Joseph Leilua crossed not long after, and put the home side ahead 12-0.
After a scrappy ten minutes from both sides, James McManus crossed in the corner after picking up a loose offload, this time Roberts was unsuccessful in his conversion.
There were a couple of chances for the Eels, with Harrison and Toutai nearing the line, only to be taken into touch by some desperate Newcastle defence.
The final Knights try of the half was a combination of Darius Boyd's skill and sheer luck - Dane Gagai ran 40 metres but was chased by Radradra and only just managed to offload, before Boyd kicked the ball from the ground, regathered and scored.
The Eels began their second half impressively, with Jarryd Hayne fending off two Knights defenders before chipping the ball that was gathered by Ken Sio who got the Eels on the scoreboard.
Not long after, and Beau Scott picked a hole in the Eels defence to swing the pendulum back in the favour of the Knights, scoring in front of the posts with Roberts converting.
James McManus scores after picking up a loose offload near the left edge, with Roberts missing the conversion.
Joseph Leilua scored in the corner after a dazzling piece of play, and five minutes later Akuila Uate added another second half try, putting the home side ahead 42-6.
Jeremy Smith avoided the nudie run for the Knights with a late try, with retiring Newcastle great Danny Buderus making his first conversion in his final game in Newcastle before retiring.
Jarrod Mullen scored after a late line break, with Dane Gagai missing a conversion attempt, putting the final score at 54-6.
The Eels have an injury cloud over Daniel Harrison, with the centre being helped from the field with what looks like a knee injury.
Newcastle Knights: 54 (McManus 2, Leilua 2, Roberts, Boyd, Scott, Smith, Mullen, Uate tries)
Roberts 6, Buderus, conversions)
Eels 6 (Sio try, Paulo goal)