The striker did the majority of the damage as Posh boss Darren Ferguson celebrated a victory over the club he left to take up the London Road hotseat back in February.
Mackail-Smith needed only 85 seconds to break the deadlock, although the visitors had every right to feel aggrieved at falling behind.
Posh wideman George Boyd clearly used an arm to control the ball before delivering the left-wing cross from which Mackail-Smith planted a powerful header into the corner.
Boyd contrived to squander a golden opportunity to double the lead moments later before Red Dragons stopper Anthony Williams made a smothering save after a lightning raid from Mackail-Smith.
His strike partner Aaron Mclean was unable to convert a Chris Whelpdale cross at full stretch before the visitors showed glimpses of potential going forward.
Chris Llewellyn saw a low drive deflected just wide before wideman Matty Done was denied by a fine last-ditch tackle from home defender Claude Gnapka when preparing to pull the trigger.
But all Wrexham's promising work was undone when Mackail-Smith gratefully doubled the Posh lead in farcical fashion four minutes before the break.
Keeper Williams charged from his area and clattered into captain Richard Hope, leaving both men on the deck as the Posh hitman walked the ball into the gaping net.
If those two goals had both featured an element of good fortune, Mackail-Smith's third strike after 53 minutes was all about quality.
He collected a clever through pass from Boyd, burst into the box and beat Williams with a fierce 15-yard finish.
Substitute Neil Roberts prodded a Wrexham consolation goal after 66 minutes, but Posh top scorer added the final gloss to their victory when slamming home three minutes from time.