Trailling by 19 points at the last change, the Bombers kicked the only three goals of the final term before the Blues held firm and won 5.2 (32) to 4.7 (31) on Sunday at Port Melbourne.
WATCH IN THE VIDEO ABOVE: Carlton seals thrilling win over Essendon
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Jo Doonan had the last two shots at goal of the game, but the first hit the post and the second also missed with 35 seconds left.
Captain Kerryn Peterson then took the kickout and after her long bomb to a crowded wing, Carlton were able to close out the match.
In the first AFLW match between the two clubs, Blues star Darcy Vescio proved the difference with her three goals.
All eyes were on Essendon star Maddy Prespakis and, to a lesser extent, Georgia Gee after their high-profile move from Carlton to the expansion club.
A Prespakis goal in the last term brought Essendon to within three points of her old club and she joined Carlton’s Mimi Hill with a game-high 21 possessions, while Gee had 10 disposals.
But Prespakis was left rueing a rudimentary error at the end of the first term.
She had a long-range set shot on goal and went to move off her line as she took the kick.
The problem was, the quarter-time siren had sounded and so Prespakis was not allowed the shot.
Indeed, for the first three terms Essendon looked every bit a first-year club as the Blues took control, extending their lead at every change.
But while Essendon conceded two goals in the third quarter, they were starting to even up clearances and contested possessions.
That set the scene for an absorbing final term, where the Bombers had the first 13 possessions and kicked three goals in the opening few minutes to pile the pressure on Carlton.
The Blues then held their nerve, with three-time All-Australian Peterson moved from her surprise role on the wing to her usual defensive post in the last term.