With the game deadlocked at 2-2 after 75 minutes, the former Peterborough striker failed to beat Paddy Kenny time from 12 yards.
The 28-year-old had opened the scoring by slamming in a first-half spot-kick and put his side ahead in the 48th minute, either side of in-form El-Hadji Diouf equalising with his second goal in as many matches from 12 yards out after Luke Varney, keeping top scorer Luciano Becchio on the bench, was brought down in the area.
Leeds levelled in the 66th minute as substitute Becchio made an impact with his first touch, seeing the ball deflect off his knee and into the net from Michael Brown's curling effort.
The Seagulls made their early dominance count in the 16th minute when Mackail-Smith emphatically converted from the penalty spot following Lee Peltier's clumsy tackle on the lively Will Buckley.
Mackail-Smith almost netted a second three minutes later, only to see his shot from the edge of the area deflected on to the upright.
Leeds started to settle and got their reward after 37 minutes. Bruno needlessly fouled Varney in the area and after referee Lee Mason pointed to the spot again, Diouf slammed in his fifth goal of the campaign.
Mackail-Smith was close to putting his side ahead, but his shot on the turn was deflected just wide.
However, the lively marksman got his second two minutes after half-time when he fired in from Buckley's pull back and almost completed a treble 14 minutes later, although Kenny was equal to his 18-yard drive.
Leeds levelled when Brown's curling effort found the bottom corner via a deflection off Becchio, who had just come on for Varney.
Mackail-Smith wasted the chance for a hat-trick 15 minutes from time when he missed from the spot after he was fouled by Sam Byram, with Kenny holding on diving to his right.
And Mackail-Smith was again brilliantly denied by Kenny late on from close range as Leeds made their point.