Goals from Taelor O’Kane and Jon Ustabasi, either side of Harry Cardwell’s equaliser, were enough to give the Coasters the spoils.
Adam Murray made three changes from Tuesday’s defeat at Solihull Moors with O’Kane, Owen Evans and Gold Omotayo coming in for Luke Conlan, Danny Philliskirk and Luke Charman.
His players made the perfect start to the game when, after just two minutes, Nick Haughton’s corner found an unmarked O’Kane and he headed into the top corner.
A second nearly arrived after Josh Kay set Ustabasi free down the right, but he saw a shot eventually cleared off the line.
Chances continued to come for the Coasters as Omotayo did well to hold off Ollie Kensdale before finding Haughton, who curled a shot inches over the home goal.
The hosts hadn’t seen many chances fall their way before Jack Wood was thwarted by the boot of Fylde keeper Theo Richardson, sending them into the break with a slight lead.
Whatever Southend boss Kevin Maher said to his side at the interval, it seemed to have done the trick as a long ball upfield was pounced upon by Cardwell, who slotted it into the bottom corner.
However, Murray’s men continued to fight and retook the lead when Kay saw Ustabasi racing past Jason Demetriou before using his pace and lifting the ball over keeper David Martin.
Emeka Obi then almost added a third after controlling superbly from a Kay corner and volleying towards the top corner, forcing Martin into a good fingertip stop.
At the other end, Southend thought they had an equaliser in the dying embers, only to be denied by Sam Graham’s solid header off the line which ensured three points for Murray’s players.
Southend United: Martin, Kensdale, Bridge, Husin, Cardwell, Mooney, Wood (Powell 83), Miley, Fonguck (Vilhete 62), Demetriou, Coker. Sub not used: Taylor.
AFC Fylde: Richardson, Gordon, Graham, Obi, Evans, Ustabasi, Whitehead, O’Kane (Philliskirk 64), Haughton (Conlan 64), Kay, Omotayo (Charman 74). Subs not used: Barrett, Ligendza.