Kevan Hurst sent the Shrimpers on their way against his former side by opening the scoring in the 28th minute.
The winger was picked out by a low left-wing cross from Anthony Straker and made no mistake with an assured close-range finish for his 10th goal of the season.
Southend, who have now lost just once in 15 games, then doubled their lead in the 59th minute when some neat passing resulted in Michael Timlin teeing up Ryan Leonard, who sped half the length of the pitch before prodding the ball past Chesterfield goalkeeper Tommy Lee.
The Shrimpers were celebrating again just two minutes later when Barry Corr lifted the ball over the advancing Lee with a cool finish.
Chesterfield's frustration increased in the 69th minute when Marc Richards saw a penalty pushed around a post by Southend goalkeeper Dan Bentley, who then also superbly denied Dan Gardner with a stunning save.