Knight-Percival header the difference as Blues suffer home defeat to the Shrews.
One goal was enough for Shrewsbury, who left Roots Hall with all three points thanks to a goal from Nathaniel Knight-Percival.
Phil Brown kept faith with the side who earned a 2-0 home win over Peterborough United last weekend, with David Mooney partnering Noel Hunt in attack.
In a first half of few clear-cut chances, both goalkeepers were on hand to rush from their goal-line to quash any potential danger.
Inside five minutes, Anthony Wordsworth lifted the ball over the top of the Shrewsbury back-line, requiring Jayson Leutwiler to be alert and clear.
Tyrone Barnett then looped a cross over to Shrews defender Matt Tootle, who lashed over with Ben Coker applying pressure.
Shrewsbury’s Knight-Percival then picked up a yellow card for a foul on Hunt with the Irish forward breaking clear on goal.
Mark Ellis scuffed an effort into the arms of Daniel Bentley just moments after Larnell Cole had blasted over, as the visitors enjoyed a spell of dominance.
Blues captain John White provided a crucial last-ditch block, after Barnett had worked an opening and got into a one-on-one situation with Bentley.
The second half saw Southend start on the front foot, with Adam Barrett swivelling in the penalty area and firing wide before Wordsworth whipped an effort past the far post following a lay-off from Hunt.
Glen Rea went into the book for a scything challenge, just a minute before the visitors broke the deadlock when the aforementioned Knight-Percival headed in at the far post from a Liam Lawrence free-kick.
Stephen McLaughlin then replaced Michael Timlin in Phil Brown’s first change of the afternoon, before Jack Payne replaced Coker six minutes later.
Blues were now playing a 3-4-1-2 formation, with Rea, Barrett and White in defence, with David Worrall, Ryan Leonard, Wordsworth and McLaughlin in midfield and Payne behind Hunt and Mooney.
Barnett made it two Shrewsbury players in the book in the 73rd minute, after a late lunge brought Leonard down.
As the Shrews looked to double their advantage, Barrett blocked an effort from Cole before Joe Pigott replaced Hunt in Southend’s final change of the afternoon.
Jordan Clark then took aim from range, but failed to trouble Bentley in the Southend goal.
Shrews boss Micky Mellon made his first change in the 83rd minute, with Jean-Louis Akpa Akpro replacing Barnett for the visitors.
The substitute managed to work his way into referee Dean Whitestone’s book almost immediately, after kicking the ball away in frustration.
A second change soon followed, with James Collins replacing Cole with three minutes remaining.
Bentley then made a great reflex save at his near post to prevent Shrewsbury doubling their advantage, when Akpa Akpro powered a strike at goal.
The Blues stopper followed it up with another two fine saves, denying both Akpa Akpro and Collins in a matter of seconds.
Blues attempted to lay siege to the Shrewsbury goal in five minutes of added time, with Wordsworth nodding down for Pigott, whose effort was crowded out in a busy penalty area.
Two consecutive corners followed, with Blues keeper Bentley going the charge as Southend chased a late equaliser.
Their late effort was unsuccessful, meaning that Shrewsbury Town left Roots Hall victorious.
Southend United: Bentley; White, Rea, Barrett, Coker (Payne - 66’); Leonard, Wordsworth, Timlin (McLaughlin - 60’), Worrall; Mooney, Hunt (Pigott - 77’).
Unused Substitutes: T. Smith, O’Neill, Bolger, Deegan.