Posh, needing to bounce back after Saturday's disappointing FA Cup exit against West Brom, and already missing Wales international defender Craig Morgan through suspension, suffered an early blow when skipper Micah Hyde limped off after eight minutes with a recurrence of a hamstring injury.
But boss Darren Ferguson clearly had his men wound up and Posh grabbed a 22nd minute lead with Charlie Lee controlling a poor clearance and sending a left-footed volley in off the foot of Andy Warrington's left-hand post for his eighth goal of the campaign.
The home side's injury luck went from bad to worse with Chris Whelpdale and Kieran Charnock having to be replaced in the space of four minutes before the break by Claude Gnapka and Tom Williams.
Yet in the second period Rotherham put surprisingly little pressure on the makeshift home defence with Posh goalkeeper Joe Lewis not severely tested apart from punching away a succession of long-range crosses, being aided by some wayward shooting by Ryan Taylor and Ian Ross.
Taylor pulled one back for Rotherham in the first minute of added time, but by then it was too late and Mackail-Smith still made sure Posh had the last word after Dean Keates flicked on.