Goals from Nicky Bailey, Gary Hooper and Leon Clarke saw the visitors stretch their run to five games without a win.
The highlight of an uneventful opening period was a decent save from Crewe keeper Ben Williams to deny Mark Gower.
But the custodian was picking the ball out of the back of his net on 17 minutes as the Shrimpers took the lead.
Leon Clarke passed to strike partner Hooper and he laid the ball off to Bailey on the edge of the box.
The midfielder's shot went into the top left corner for his fourth goal of the season.
Two minutes later the Railwaymen thought they had got on terms when Julian Baudet's close-range header from Ryan Lowe's free-kick was ruled out for offside.
Crewe failed to test Blues keeper Steve Collis in the remainder of the half, while the hosts should have doubled their advantage when Tommy Black's deflected shot was saved one-handed by Williams but Hooper could only blaze over with the goal at his mercy.
Gary Roberts unsuccessfully appealed for a penalty following a challenge from Adam Barrett.
And three minutes after the restart Blues appealed for a penalty after Billy Jones' challenge on Black, but referee Andy Penn waved them away.
Mark Gower and Peter Clarke both went wide before Southend doubled their advantage through Hooper on 63 minutes.
Leon Clarke's initial shot from Hooper's pass was parried by Williams and Hooper raced in to lash home the loose ball for his first goal of the season.
Leon Clarke made sure of the points from the penalty spot on 82 minutes after Hooper was brought down by Williams. It was the on-loan forward's sixth goal for Blues.
Despite playing three men up front, the Railwaymen struggled to put any real pressure on the home goal.