After Joe Daniher and Cale Hooker were held goalless in the first half, Collingwood stuck with the Lynden Dunn (Hooker) and Tyson Goldsack (Daniher) match ups.
After the Pies kicked the first goal of the half, Essendon responded with the next two, including one kicked by Hooker.
The second came after Zach Merrett was taken from the field following an incident with Levi Greenwood.
Collingwood responded with the next three in just six minutes while Merrett was off the field to cut the margin to 15 points midway through the third term.
Tension lifted in the match with Brayden Maynard and Orazio Fantasia clashing on the wing. Collingwood were awarded the free kick, but a short time later Fantasia kicked his fourth to steady the ship for the Dons.
Merrett returned nearing three quarter time and set Daniher up for his first goal of the game.
At the final change Essendon led by 23 points.
Just 21 seconds into the last quarter Merrett kicked his second goal to stretch the margin to 29 points.
And when Fantasia kicked his fifth of the match a minute later, the lead was 35 points.
In a blistering start to the last term Essendon had 18 of the first 20 possessions and kicked three goals in this period, with Daniher booting the third goal in that burst to put the Dons in front by 43 points.
Collingwood kicked a couple late but the Dons efficiency all over the ground was key factor in a crucial win for the Club.