Makeshift striker Bilel Mohsni was sent off after being booked for a foul in the 54th minute and receiving a second yellow card for dissent 23 minutes later.
But Gillingham were unable to make their numerical supremacy count and paid the price in the 87th minute, when Mark Phillips headed home from close range from a Ryan Hall corner.
Gillingham's Luke Rooney was denied by Glenn Morris and the Southend goalkeeper parried a Joe Martin effort before Mohsni cleared.
Southend's best chances in the first half fell to Blair Sturrock, who had a volley tipped onto the bar by Ross Flitney, before the goalkeeper smartly saved a 30-yard effort from Ryan Hall.
In the second half, Flitney denied saved Mohsni's angled drive but Andy Hessanthaler's visitors replied, with Luke Rooney, Danny Kedwell and substitute Steffan Payne all being denied by Morris.
Referee David Phillips played five minutes of stoppage time but Southend held out to return to winning ways following their 2-0 defeat to Swindon on Saturday.
Gillingham last week