Golden boy Boyd broke the deadlock two minutes after the interval and Mackail-Smith made sure of an historic success in the first-ever Football League meeting between the two clubs when firing home in stoppage time.
Leeds had the lion's share of the possession but the best chances fell to Posh in an often flat first period.
Mackail-Smith was denied on numerous occasions by Leeds keeper Casper Ankergren - the Dane stepping into the side at short notice after David Lucas suffered a finger injury in the warm-up.
The best of the more limited Leeds chances fell to Luciano Becchio who headed wide from an early free-kick and then saw a 20-yard lob beat home goalkeeper Joe Lewis but drop wide of the far post.
But the deadlock was swiftly broken in the second period as Posh got their noses in front. Boyd turned in his fourth goal of the campaign after winger Dominic Green - making his full debut - had drilled a deep Russell Martin delivery back across the face of goal.
Andy Robinson almost replied instantly with a fierce 25-yard drive that arrowed just wide of the far post before Posh keeper Josh Lewis denied the prolific Jermaine Beckford.
Leeds thought they had hauled themselves level nine minutes from time when Becchio pounced on a rebound after Lewis spilled a drive from substitute Neil Kilkenny.
But the assistant referee's flag came to Posh's rescue and the hosts made the most of the reprieve to double their lead at the death when Mackail-Smith beat Ankergren from eight yards after Boyd had sent another Martin cross into his path.