The Aberdeen striker scored a goal in each half to deprive Hibs of the point they needed to secure a UEFA Cup slot.
Hibs still have a superior goal difference going into the final weekend of the season but Aberdeen have given themselves hope of sneaking in the back door.
It was a deserved win as Aberdeen dominated possession and had the more inventive players although Derek Riordan missed a penalty for Hibs and Gary Smith struck the post in stoppage time.
Hibs threatened first and Stephen Glass' eight-minute free-kick was spilled at his right-hand post by Ryan Esson but Markus Heikkinen managed to hook the loose ball to safety.
But that was a rare flurry around the Aberdeen goalmouth in a first half which was dominated by Jimmy Calderwood's side.
With Scott Severin pulling the strings in midfield, Aberdeen built patiently but their intent was clear when they were within sight of goal.
Mackie wasted a good early chance when Lubomir Blaha knocked the ball into his path but he fired well over the bar.
The Dons striker then fashioned a chance for himself when he hooked the ball over Gary Caldwell's head but his final shot was just a couple of yards wide.
There was a brief response from Hibs midway through the first half when Amadou Konte and Garry O'Connor combined but O'Connor's final 25-yard shot was over-ambitious and wayward.
There was an anxious moment at the other end when Zander Diamond managed to get his head to a Severin corner at the near post and Simon Brown juggled the ball in his six-yard box before finally securing it.
But Aberdeen made the breakthrough in the 28th minute after hesitancy in the Hibs defence. Scott Muirhead's corner was knocked back into the six-yard box by Severin and Mackie stuck out a boot to divert it into the net.
Hibs had a chance to equalise three minutes before the break when Michael Hart gave up possession and the ball broke to Ian Murray but his shot was too close to Esson.
The home side squandered an even better chance at the close of the half. Diamond fouled Scott Brown in the penalty area for an obvious penalty.
Riordan stepped up to take the spot-kick but Esson dived to his left to pull off a terrific save and keep Aberdeen in front at half-time.
Riordan made amends six minutes after the restart. Aberdeen failed to deal with a throw-in from Ian Murray and, as Heikkinen dallied over his clearance, Riordan nipped in to stab a ten-yard shot past Esson.
O'Connor then tried his luck with a near-post header but it did not have the power to beat Esson.
Aberdeen responded and a great run and shot from Muirhead brought a fine save from Simon Brown who pushed the ball away for a corner.
It was a lively encounter with chances at both ends. Konte had a chance for Hibs after cutting inside Diamond but Esson was alert to the danger and saved at the striker's feet.
Aberdeen restored their lead in the 70th minute when Muirhead's shot broke to Mackie who headed the ball home from six yards as the Hibs defence stood appealing for offside.
Hibs threw everyone forward in the closing minutes and a Smith header struck the post in a goalmouth scramble but Aberdeen held on for the three points.