The home side scored two tries in the first six minutes to Jamie Lyon and Glenn Stewart to race out to a 12-0 lead.
Kevin Naiqama hit back for the Knights in the 13th minute, but from there the first half was all Manly as they opened up a 34 point lead at halftime in a highly entertaining display of rugby league which included two tries in 10 minutes to Tony Williams and two tries in four minutes to Brett Stewart.
Williams threw off Jarrod Mullen for his 17th minute try, then Kieran Foran scored after Jamie Buhrer broke through the Knights defence in the 22nd minute.
Canterbury-bound Williams then pounced on a Foran grubber for his second try in the 27th minute.
Stewart then scored from a brilliant 50m scything run in the 32nd for his almost mandatory Brookvale Oval four-pointer, before the fullback crossed again four minutes before halftime - beating the Knights defence close to the line.
The 38-4 scoreline at the break summed up the home side's complete domination.
But injuries severely slowed their momentum in the second stanza. Jason King (shoulder), Matt Ballin (calf) Jamie Buhrer (concussion) and David Williams (leg) left Manly coach Geoff Toovey without an interchange bench to turn to for the last 36 minutes as the NRL defending champions eased to their 14th win of the year.
Naiqama (51st and 63rd minute) and Jarrod Mullen (54th minute) crossed for the visitors as they attempted to make a game of things.
But the deficit proved too great and a 77th minute try to Jorge Tafua gave Manly the 22-point win.
Of further concern for Manly, Tony Williams was put on report for a possible 66th minute trip, and for the Knights Kade Snowden is also on report for a lifting tackle shortly after.
-AAP