Yet despite losing defenders John White and Matt Heath to injuries, it was Colchester boss Paul Lambert who must have wondered just how his side trailed at the break.
Pushing forward they had Posh at full stretch after just a couple of minutes with Heath and Jermaine Easter getting in shots before the ball was eventually scrambled clear.
On the half-hour, Easter's low cross from the right found a way through only for Clive Platt to fail to connect. Then David Perkins fired across goal with Russell Martin and Tom Williams managing to clear.
Mackail-Smith, who did not make the most of a couple of openings, curling one wide of Dean Gerken's left-hand post and then shooting tamely after a solo run, finally hit the target in first-half stoppage time.
The nippy frontman grabbed his 14th goal of the season from inside the area after Boyd undid Colchester with a superb ball over the top.
Platt hauled Colchester level on 61 minutes, netting against one of his former clubs with a close-range header after reaching a deep cross from Perkins, but Posh were back in front within two minutes.
Gerken did well to keep out a Gabriel Zakuani header after Colchester struggled to clear following a corner and the ball went only as far as Boyd who claimed his sixth goal of the campaign with a low left-footed drive from a dozen yards.
Colchester's defensive woes were compounded after 65 minutes when White's replacement, Lee Hills, also limped off.