The Sky Blues paid the price after Gary McSheffrey's 56th-minute penalty was saved by veteran goalkeeper Maik Taylor, the clearest of several openings fashioned by the wasteful hosts on Tuesday night.
And defender Lowry popped up just 10 minutes later to head home Alan Dunne's right wing cross and leave City staring at third tier football for the first time since 1964.
Coventry now find themselves five points adrift of fourth-bottom Bristol City with just two matches remaining - Saturday's home fixture against already-relegated Doncaster and a daunting final day trip to high-flying Southampton.
A disastrous season, and a potentially bleak future, for the cash-strapped club could well be sealed at the weekend, but Andy Thorn's side will continue to battle while there remains hope - with famous relegation escapes firmly etched in the Coventry's past.
For Millwall, who secured their own Championship status at the weekend, it was a fourth successive victory for the first time in over two years.
Sky Blues skipper Sammy Clingan summed up the size of the clash in his programme notes when he admitted his side needed the three points.
Yet the hosts were slow to rise out of the blocks, Millwall's on-loan Tottenham striker Harry Kane - with three goals in his last three goals - firing wide within the opening minute.
Cody McDonald replied at the other end before a nervy City created a clear opening, Clive Platt heading over Clingan's inch perfect cross from close range when he should have at least hit the target.
Kane again curled narrowly off target after some more neat approach play from a dominant Millwall.
But Coventry got a foothold on proceedings as the first half wore on and a fired up Clingan tested Taylor with a retaken free-kick before midfield partner Oliver Norwood blazed over when well placed having been teed up by Platt.
Taylor then keep out McDonald's volley with a superb reflex save after McSheffrey's initial effort had been blocked.
Coventry started the second half on the front foot but McDonald could only fire another opportunity over after being given a clear sight of goal by Platt's flick-on.
Yet the clearest of all openings came in the 56th minute as McDonald robbed possession on the left and burst into the area before being brought down by Taylor, however the 40-year-old stopper redeemed himself as he dived to his right to palm away McSheffrey's spot-kick.
And the magnitude of the penalty failure was emphasised 10 minutes later as Lowry headed home Dunne's sweet delivery from the right.
Andy Keogh and James Henry wasted great chances to sow matters up for the visitors.
But it did not matter as Coventry were unable to fashion an equaliser, leaving them facing an extremely tall order if they are to avoid relegation 11 years after they dropped out of the Premier League.