It was a slow start to the match with the first corner arriving in the 18th minute to Preston and it was the 21st minute before the first chance of the game, when Simon Whaley had a 25-yard right-foot shot which Southend keeper Darryl Flahavan dived low to his right to save.
Brett Ormerod had a goal ruled off-side after 28 minutes and the ever dangerous Jamal Campbell-Ryce had a good run and a 20 yard right-foot shot saved by home keeper Andy Lonergan after 32 minutes.
Danny Pugh hit a 20-yard left-foot shot both over and wide of the right-hand post.
Chris Sedgwick lost the ball to Matt Harrold and he should have done better but Lonergan saved.
After just 36 minutes Freddy Eastwood had to go off and was replaced by Richie Foran.
Southend took the lead in the 41st minute when a Campbell-Ryce cross was cleared by Sean St Ledger, but Alan McCormack found Kevin Maher and he hit a 20-yard right-foot shot into the keeper's top left-hand corner of the net.
St Ledger equalised with a close-range header in the 50th minute, his first goal for Preston from a Chris Sedgwick left-wing right-foot corner.
Seyfo Soley was booked for a foul and Steven Hammell had a free-kick tipped over the bar by Lonergan, before Pugh cleared off the line from a Harrold shot.
Campbell-Ryce was booked for a dive in the box and then Whaley was replaced by Patrick Agyemang.
Sedgwick was booked for a foul on MCormack and Daniele Dichio replaced Ormerod.
Peter Clarke handballed a Dichio shot and Graham Alexander took the penalty and hit it high into the roof of the net right-footed to make it 2-1 to Preston.
Lewis Neal replaced Sedgwick and Hammell was booked for a foul on Nugent.
With two minutes to go Mark Gower found ex-Preston midfielder McCormack and he hit a 25-yard right-foot volley into the keeper's top left-hand corner of the net.
Into added time Maher hit a 25-yard chip and that went into the top left-hand corner of the net to make it 3-2 to Southend.