Tom Ince scored his first goal in six games to spark the comeback that secured father Paul's first win as Blackpool manager.
The Tangerines were trailing at half-time thanks to Cristian Battocchio's delightful opener and the hosts felt aggrieved not to be further ahead after they had two penalty claims rejected. But they were guilty of some errant finishing throughout and were made to pay eventually when the England Under 21 international levelled things up.
The former Liverpool winger also played a part in MacKenzie's decisive winner to record only Blackpool's second league win in their last eight outings.
Watford boss Gianfranco Zola made five changes to the side that beat Sheffield Wednesday in midweek. Joel Ekstrand, Marco Cassetti and Nathaniel Chalobah were all ruled out with injury while Almen Abdi and top-scorer Matej Vydra also missed out.
Lloyd Doyley, Fernando Forestieri and Matthew Briggs were amongst those recalled, while Paul Ince made just the one change, striker Matt Derbyshire replacing the injured Gary Taylor-Fletcher.
The Hornets hit the ground running, spurning a couple of early chances to break the deadlock. First Jonathan Hogg, a late replacement for Abdi who suffered an injury in the warm up, headed inches wide of the post after a terrific cross by Ikechi Anya.
The breakthrough came on 27 minutes when Troy Deeney seized on an error by MacKenzie. Forestieri's quick throw caught the defender unaware, setting Deeney through on goal. The former Walsall striker looked to be shaping up for a shot before he unselfishly rolled the ball across for Battocchio, who chipped a cheeky finish over goalkeeper Matt Gilks.
The home supporters were incensed seconds before the break when Deeney, seemingly through on goal, was hauled back as he lined up the shot but the referee waved play on.
Blackpool looked a little more positive after the break but it was the hosts who continued to look the more threatening on goal.
Battocchio fired wide from the edge of the box before Briggs glanced his header wide unmarked at the back post from Anya's free-kick.
But the Seasiders continued to dominate possession and got their reward on 76 minutes. Left-back Stephen Crainey made a darting run before picking out Tom Ince at the near post who steered an expert finish across the body of Jonathan Bond and into the far corner.
Zola's side threw away the lead against Wolves earlier this month and were guilty of poor defending again as Blackpool took the lead two minutes from time. Tom Ince's corner wasn't cleared and MacKenzie appeared from the melee to slot the ball into the corner.