McCormack, restored to the midfield after a two-match ban, also scored twice against the Terriers in a 4-1 victory at Roots Hall in December.
McCormack showed good energy when he sprinted clear three minutes into added time, shrugged off two defenders and fired past keeper Matt Glennon.
Before then it had seemed Huddersfield had claimed a point from a scrappy game which was spoiled by some strange decisions from referee Mike Pike.
Hal Robson-Kanu, 18, on loan from Reading, put Southend ahead five minutes before the break, for his second goal in two starts.
Tommy Black did well to keep the ball in play on the far touchline and rolled a pass for Robson-Kanu who side-stepped Michael Collins and fired through the legs of both Rob Page and Nathan Clarke. The shot deflected slightly off Clarke and Glennon was unsighted.
Huddersfield were booed off at half-time but improved after the interval. Veteran striker Andy Booth ran himself into the ground and snatched the equaliser in the 73rd minute, just moments before he was about to be replaced.
Boss Andy Ritchie had strikers Luke Beckett and Danny Broadbent ready to come on and the Town boss confirmed afterwards that Booth was one of those to be subbed.
Booth rose well to power home a header from a Robbie Williams corner and that looked to be enough to clinch a point.
Southend skipper Adam Barrett had a header cleared off the line by Malvin Kamara with the 90 minutes up.
Poor Huddersfield defending late in the game allowed McCormack to race through from midfield and fire in off the post for the winner to fuel Southend's play-off push.