But the former Dagenham striker was told by boss Darren Ferguson afterwards that he should have had a hat-trick.
Mackail-Smith's goal on 58 minutes when he burst through the back four before slotting home looked like easing Peterborough to a comfortable victory.
But after a Brentford fightback, Mackail-Smith missed two golden chances to seal victory in the last ten minutes.
First he fired wide with the goal at his mercy and then, with just minutes left, he forced Bees keeper Simon Brown into a brilliant one-handed save.
Aaron McLean gave Posh the lead with a tenth minute header from Claude Gnapka's cross.
By that time Glenn Poole had already shot inches wide for Brentford and Josh Low had been foiled by a brilliant Brown save.
Alan Connell then fired a free-kick wide after Poole was fouled and, at the other end, George Boyd fired wide from the edge of the box.
As the half drew to a close, Nathan Elder saw two good headers saved as Brentford looked to pull level.
However, Posh looked the more likely scorers after the break with Brown making a great save from Mackail-Smith and a last-ditch Alan Bennett tackle denying the same striker.
Mackail-Smith finally got the goal he was itching for on 58 minutes, but just four minutes later Connell pulled one back for the Bees finishing well from Ryan Dickson's cross.
Poole saw a shot saved after a brilliant flowing move as Brentford pushed for an equaliser, but it was the visitors who should have made the game safe with Mackail-Smith's brace of misses.
It was an eighth successive victory for Posh and saw them overtake MK Dons at the summit of League Two after just one day at the top for Paul Ince's side.