Coming off a first defeat in 35 games, North overturned a 17-point quarter-time deficit to win 10.5 (65 to 5.4 (34) at Ikon Park on Friday.
With both teams now having a 7-1 win-loss record, victory lifted North above Melbourne into top spot on percentage.
North slammed on nine successive goals between the second and fourth quarters after kicking just 0.2 in the first term.
They shut down the Dees in the middle quarters, limiting them to a single behind in each, to lead by seven and 19 points after the second and third term, respectively.
"At quarter-time, we've been in this position before, so just really proud of the group,'' North Melbourne ace Jasmine Garner told 7, Fox and Kayo.
"The hunger was there, the drive was there, it's a bloody great win.
"it was a weird week to be honest, it was like COVID days again, flu has gone through the group.
"We were really looking forward to the challenge coming off a loss last week, and as a group and as a midfield group we really wanted to respond, and I thought we did that tonight."
Melbourne kicked three goals in the first quarter, the last coming from captain Kate Hore in her 100th game for the Dees.
North forced them to go wider In the second quarter, feasting on turnovers and kicking four goals for the term.
The Kangaroos kicked the only two goals of the third quarter, and Garner settled the contest with two more early in the last, before Mia Austin bagged two late majors for Melbourne.
The Demons had as many inside-50s as North from the end of the first quarter until well into the fourth, but couldn't manufacture enough scoring opportunities under pressure.
Garner, Ash Riddell and Jenna Bruton all finished with more than 30 possessions, and Eilish Sheerin logged 26 touches and match highs of 11 tackles and 10 clearances for the Roos.
For Melbourne, Tyla Hanks gathered 32 disposals and Austin led all scorers with three goals.
North star Taylah Gatt, playing her first game of the season, went to the bench early in the final quarter with an ankle injury.
Melbourne's Shelley Heath-Barker spent most of the second half on the bench after suffering a calf injury.
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