From Marzhew's first try after eight minutes, the Dragons were never really in Saturday's contest, and will finish the weekend two wins behind the team in second-last.
The winless Dragons went to half-time down 32-0 in Wollongong, even further behind than against the Sydney Roosters in their 62-16 loss on Anzac Day.
That last-start defeat could be at least partially explained by an abrupt preparation that involved the axing of coach Shane Flanagan five days before kick-off.
But Saints were similarly hapless in Dean Young's second game as interim coach, which came after a full fortnight's preparation during the bye.
Injuries to Moses Suli (back) and Dan Atkinson (hand) brought Lyhkan King-Togia into the halves and pushed Clint Gutherson from fullback to centre before kick-off.
In his 150th game, fullback Kalyn Ponga helped the Knights eviscerate both makeshift edges, with the visitors particularly adept at attacking from long range.
The Knights exposed King-Togia and out-of-sorts Val Holmes on the left edge and Kade Reed proved a popular target on the other side of the field.
Ponga breezed straight past the second-gamer as he put Dylan Lucas over for the fifth of Newcastle's six first-half tries.
Stopping a fully-loaded Knights side was always going to be difficult, but the Dragons did little to help themselves.
King-Togia threw an intercept pass for Bradman Best to score an 80-metre try that reminded NSW coach Laurie Daley of his State of Origin credentials.
Marzhew had his second try by flopping over from dummy-half in the first half, to the embarrassment of Gutherson and Reed defending the tryline.
The left winger had back-to-back hat-tricks after crashing past Setu Tu on the last tackle midway through the second half, and a first four-try haul thanks to Best's flick pass.
His fifth came in the final minutes sprinting into open space at close range.
The Dragons had two second-half tries off grubber kicks to the right edge.
Left winger Mat Feagai went off injured with a back injury during the closer second half and faces an unclear return date.
But the bigger question is when a first win of the season can realistically come for the Dragons, who haven't tasted victory since early August.
Before their next bye, the Dragons face top-four sides Penrith and the Warriors before meeting reigning premiers Brisbane and then perennial contenders Cronulla.
Only one of their next six games will be played at home.
The win continues the Knights' turnaround under first-year Justin Holbrook, who has helped the reigning wooden spooners to a 6-4 record.
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