It was the first rugby league game to be held in Belfast since Ireland hosted Samoa at Windsor Park in the 2000 world cup.
The Wolfhounds, therefore, missed out on the chance to secure the Alitalia European Cup, having beaten Scotland in the three-way tournament - preparation for next year's Rugby League World Cup - last Sunday in Edinburgh.
The match began at a frenetic pace, and Ireland handled the first couple of attacks from England, but failed to gain much ground on their own second set of six and had to kick from deep.
From the resulting pressure the visitors launched a move down the left and winger Jodie Broughton opened the scoring in the third minute, before half back Luke Gale's kick slipped wide.
But the home side responded well.
In the eighth minute England full back Chris Riley ran back a kick but a good defensive chase and some tough tackling put him under pressure and forced a fumble.
Ireland skipper Liam Finn dived on the ball and suddenly the Wolfhounds had a set of tackles deep in Knights territory.
An assault down the right saw winger Tim Bergin go close, before the Wolfhounds moved left with some crisp passes.
With the defence stretched, centre Joshua Toole was able to go between two opponents out wide for the try, but the conversion was missed leaving the score at four apiece.
For the next fifteen minutes Ireland were very competitive.
The physically bigger Knights set our their stall with a direct approach, but the home side tackled well and, when they had the ball, attacked creatively through Finn and James Mendeika.
England however were getting the better of both possession and territory, and they were next to score.
A poor clearance kick from Wolfhounds hooker Carl Sice was run back with purpose by the visitors, with right wing Kieron Dixon crossing out on the right after a couple of tackles.
Indiscipline crept into the home side's game during the remainder of the first half and was punished. Tries from Jordan Turner, Tom Burgess and Daniel Houghton helped the Knights to a 26-4 lead at the break.
The second half started with a period of heroic defence from Ireland, with brave work from all the players including Greg McNally, Colton Roche and vice captain Tyrone McCarthy.
Despite having almost no possession and suffering repeated goal line drop outs as England kept hammering at their line, they held firm for the first fifteen minutes of the half.
England varied their standard, tactic of sending forwards in behind the ruck - with the enormous Burgess twins, George and Tom, rampant - by using punchy passing moves out to the wings late in each set of six.
Forwards like Elliot Cosgrove and 22-year-old Matty Hadden, who spent last summer playing for Antrim Eels, put their bodies on the line in a bid to hold out the visitors.
However Jodie Broughton's second try, following a clever grubber kick angled behind the defensive line by Dan Sarginson, finally broke the resistance and more scores followed.
Michael Lawrence and both the Burgess twins - Tom with his second - crossed and, with Luke Gale's goal kicking improving throughout the game, the final score was 4-56.
Ireland team: (1-13) Gregg McNally, Tim Bergin, Stuart Littler, Joshua Toole, John O'Donnell, James Mendeika, Liam Finn (c), Sean Hesketh, Carl Sice, Luke Ambler, Callum Casey, Elliot Cosgrove, Tyrone McCarthy.
Interchange: (14-17) Colton Roche, Wayne Kerr, Matty Hadden, Sam Wellens.
England Knights: (1-13) Chris Riley, Kieron Dixon, Jordan Turner, Rhys Evans, Jodie Broughton, Dan Sarginson, Luke Gale, Scott Taylor, Daniel Houghton (c), George Burgess, Jack Hughes, Michael Lawrence, Michael Cooper.
Interchange: (14-17) Tom Burgess, Shaun Lunt, Chris Clarkson, Ben Jones-Bishop.