The Demons killed off the contest with the first six goals and gave their percentage a healthy boost with Saturday night's 22.7 (139) to 7.7 (49) win at the MCG.
Comben, 21, was hospitalised with a broken leg and is likely to undergo surgery to have a plate inserted.
Comben, who has a history of left leg injuries, was hurt when he went for a mark in the opening quarter.
Play was held up for several minutes and, significantly, the Seven Network opted against showing a replay of the gruesome incident.
Demons coach Simon Goodwin started his post-game media conference by wishing Comben and his family well.
North coach Alastair Clarkson confirmed the outlook is grim for Comben, but hopes he will return later this season.
"I was told on the bench he has a fracture to his lower leg, it will require some surgery.
"They're going to probably put a plate in of some description.
"That's a blow to us, he's a young guy trying to make his way in the game."
Fellow North forward Callum Coleman-Jones was also forced from the game in the third term with concussion after coming off second-best in a marking contest with Demons defender Steven May.
Completing a disastrous night for the Roos, Tom Powell needed help from trainers as he went off after rolling his ankle in the last term.
It is North's biggest losing margin under Clarkson, after they won their first two games, and also Melbourne's fourth 100-plus score this season.
"It was exactly what we wanted," Goodwin said.
"We really wanted to put the defensive side of our game to them and we did that for the majority of the night."
Clarkson noted that Melbourne had as many as 10 players in their side of All-Australian quality and were just too good for the rebuilding Kangaroos.
"We came up against a bloody, really good side," he said.
"I thought we played better tonight than we had in the last two weeks - the 90-point margin doesn't suggest it.
"We competed in different areas of the game really, really well. But out of a half chance, they'd make a full opportunity and out of a full opportunity for us, we'd somehow turn it into a half or a quarter-chance.
The Dees kicked their highest score this season and were on track to their biggest winning margin against the Kangaroos, before North kicked the last three goals of the match.
Melbourne midfielder Clayton Oliver has three more Brownlow Medal votes with his 37 possessions, while Christian Petracca and Angus Brayshaw, in his 150th game, also shone.
Alex Neal-Bullen was rewarded with a goal for an outstanding run-down tackle on an unsuspecting Luke McDonald late in the second quarter.
Cameron Zurhaar kicked three goals for North, while impressive youngster Harry Sheezel and Aaron Hall had 30-possession games.
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