Kevin Maher's classy double earned Southend a vital three points as struggling Preston slipped to a fourth straight defeat.
Skipper Graham Alexander's late penalty looked to have sealed the points for Preston but Alan McCormack slammed home a volley from 25 yards two minutes from time against his old club and Maher completed a brace with two minutes of added time gone.
Paul Simpson's men have fallen away in the race for a top two place with defeats at Leeds, QPR and Crystal Palace in the space of a week.
And their problems deepened against Southend, who were three points from safety at kick-off, with Maher's crisp 41st-minute strike sending North End in behind at the break.
Sean St Ledger headed in his first for Preston just after the interval and after Peter Clarke was adjudged to have handled, the reliable Alexander made no mistake from the penalty spot with just over 10 minutes left.
But in the 88th minute, McCormack smashed home to put Southend level and a second curled strike from Maher took the points for the visitors.
Without Paul McKenna, who has been absent since February due to a groin problem, North End badly lack craft in midfield and once again they struggled to come to terms with a team that had bodies behind the ball.
In the 21st minute, North End finally forced a save from Southend goalkeeper Darryl Flahavan, although he barely tested him from 30 yards.
Southend played some bright football but Jamal Campbell-Ryce's strike in the 32nd minute was their first effort on goal and was easily dealt with by Andy Lonergan.
Southend should have taken the lead shortly after when Lonergan's throw caught Chris Sedgwick by surprise.
But, having nicked the ball from the Preston midfielder, Matt Harrold shot straight at Lonergan.
However, four minutes before the break Maher put his team in front
Campbell-Ryce's cross from the right was glanced away by Sean St Ledger but only as far as McCormack on the left.
The former North End midfielder passed infield to the unmarked Maher, who curled the ball into Lonergan's top corner from just outside the area.
Five minutes after the restart, David Nugent's glancing header allowed Sedgwick to surge into the area only to have his shot diverted wide.
From the resulting corner, Sedgwick's corner was met by the unmarked St Ledger five yards out and North End were level.
Steve Hammell's powerful free-kick was pushed away by Lonergan a couple of minutes later and from the following corner, Pugh cleared off the line from Harrold, before Peter Clarke fired just high and wide from yet another corner.
In the 77th minute substitute Danny Dichio's effort from the edge of the box hit Clarke's arm from close-range on the edge of the area and referee Andy Hall pointed to the spot.
And Alexander slammed the penalty straight down the middle to put Preston in front with his sixth of the season.
But in the 88th minute, Mark Gower's corner was only half-cleared by Preston and lurking on the edge of the box, former North End man McCormack lashed the ball into the roof of Lonergan's net.
And in the 93rd minute, space opened up for Maher, who again showed unerring accuracy to curl the ball into the top corner from more than 25 yards to leave Preston stunned.
Preston (0) 2 Southend (1) 3
Preston Lonergan, Pergl, Wilson, St. Ledger, Alexander,Whaley (Agyemang 69), Sedgwick (Lewis Neal 79), Soley, Pugh,Ormerod (Dichio 75), Nugent.
Subs Not Used: Henderson, Ricketts.
Booked: Soley, Sedgwick.
Goals: St. Ledger 51, Alexander 79 pen.
Southend Flahavan, Francis, Clarke, Barrett, Hammell,Campbell-Ryce, McCormack, Maher, Gower, Eastwood (Foran 36),Harrold.
Subs Not Used: Collis, Hunt, Bradbury, Sodje.
Booked: Clarke, Campbell-Ryce, Hammell.
Goals: Maher 41, McCormack 88, Maher 90.
Att: 13,684
Ref: A Hall (W Midlands).