After defeats in their past two League One games, Phil Brown's side took an early lead from the penalty spot when Simon Cox fired home.
Southend remain one spot and one point outside the play-off places after sixth-placed Millwall overcame Northampton, while defeat leaves Chesterfield nine points from safety with thee games remaining.
Anthony Wordsworth and Cox breached the static Spireites defence in the second half to kill the contest, while Marc-Antoine Fortune made it four with his first touch after coming off the bench.
Just before the break Dion Donohue was dismissed for a foul on Jason Demetriou to add to Chesterfield's woes.
Cox was the man that earned and scored Southend's 15th-minute penalty. On the ball, he stood firm as goalkeeper Thorsten Stuckmann scampered towards him and when contact was made the referee had an easy decision to make and the spot-kick was duly converted.
Poor defending contributed to United's three second-half goals, Wordsworth converting a Demetriou cross while Cox took advantage of some solid Will Atkinson work before Fortune slipped through a shell-shocked defence to complete the scoring.
Report supplied by the Press Association.
Match ends, Chesterfield 0, Southend United 4.
Second Half ends, Chesterfield 0, Southend United 4.
Corner,  Southend United. Conceded by Tom Anderson.
Attempt blocked. Theo Robinson (Southend United) right footed shot from the centre of the box is blocked.
Corner,  Southend United. Conceded by Paul McGinn.
Attempt missed. Liam Grimshaw (Chesterfield) right footed shot from a difficult angle and long range on the left is just a bit too high.
Foul by Paul McGinn (Chesterfield).
Stephen McLaughlin (Southend United) wins a free kick on the right wing.
Attempt missed. Michael Timlin (Southend United) left footed shot from more than 35 yards is high and wide to the left.
Liam Grimshaw (Chesterfield) is shown the yellow card for a bad foul.
Michael Timlin (Southend United) wins a free kick in the attacking half.
Foul by Liam Grimshaw (Chesterfield).
(Southend United) wins a free kick in the attacking half.
Foul by Sylvan Ebanks-Blake (Chesterfield).
Attempt missed. Anthony Wordsworth (Southend United) left footed shot from outside the box is close, but misses the top left corner.
Stephen McLaughlin (Southend United) wins a free kick in the defensive half.
Foul by Paul McGinn (Chesterfield).
Substitution, Chesterfield. Sylvan Ebanks-Blake replaces Kristian Dennis.
Substitution, Southend United. Theo Robinson replaces Simon Cox.
Goal!  Chesterfield 0, Southend United 4. Marc-Antoine Fortuné (Southend United) right footed shot from the centre of the box to the centre of the goal. Assisted by Anthony Wordsworth.
Substitution, Southend United. Marc-Antoine Fortuné replaces Nile Ranger.
Substitution, Chesterfield. Liam Grimshaw replaces Joe Rowley.
Substitution, Southend United. Zavon Hines replaces Will Atkinson.
Goal!  Chesterfield 0, Southend United 3. Simon Cox (Southend United) left footed shot from the centre of the box to the top left corner.
Attempt blocked. Michael Timlin (Southend United) right footed shot from outside the box is blocked.
Attempt missed. Anthony Wordsworth (Southend United) left footed shot from outside the box is close, but misses to the right.
Attempt blocked. Jason Demetriou (Southend United) right footed shot from outside the box is blocked.
Substitution, Chesterfield. Rai Simons replaces Dan Gardner.
Goal!  Chesterfield 0, Southend United 2. Anthony Wordsworth (Southend United) left footed shot from the centre of the box to the bottom left corner. Assisted by Stephen McLaughlin.
Foul by Nile Ranger (Southend United).
Tom Anderson (Chesterfield) wins a free kick in the attacking half.
Attempt missed. Will Atkinson (Southend United) right footed shot from the centre of the box is high and wide to the left.
Will Atkinson (Southend United) is shown the yellow card for a bad foul.
Foul by Will Atkinson (Southend United).
Daniel Jones (Chesterfield) wins a free kick in the defensive half.
John White (Southend United) wins a free kick in the defensive half.
Foul by Paul McGinn (Chesterfield).
Attempt blocked. Will Atkinson (Southend United) right footed shot from the centre of the box is blocked.
Second Half begins Chesterfield 0, Southend United 1.
First Half ends, Chesterfield 0, Southend United 1.
Southend got their play-off challenge back on track with a comfortable win at 10-man Chesterfield, who are all-but relegated.