Rhys Murphy gave the visitors the lead but Saidou Khan hit an instant equaliser two minutes later.
Debutant Luke Croll then turned the scoreline around, finishing from inside the area.
Kabongo Tshimanga came off the bench to add a third before Southend’s Sam Dalby missed an injury-time penalty.
Both sides ended a man down as Calvin Miller and Zak Brunt were sent off.
Here are Liam Norcliffe’s player ratings...
5. Jeff King 7
Him and Miller caused lots of problems on the wings in the first-half. King delivered some dangerous crosses, got into the box often and showed lots of attacking intent. He was quieter going forward after the break as Southend pressed for an equaliser. Photo: Tina Jenner
6. Manny Oyeleke 7
He did the dirty side of the game well in the centre of the park. Showed some nice composure on the edge of the box to keep the ball moving when he was urged to shoot by the home crowd in the build-up to Croll's goal. Photo: Tina Jenner
7. Jak McCourt 6
Can't fault his effort. His fierce shot at the far post was parried by Arnold and Croll scored the rebound. A bit guilty of trying to go for the spectacular at times rather than keep it simple. Subbed off with 15 to go. Photo: Tina Jenner
8. Calvin Miller 7
He was Chesterfield's best player in the first-half. He was a constant threat down the left and had the beating of Howard and White all day long. His assisted the first goal, cutting in on his right foot to deliver a deep cross for Khan to head in. He came closing to scoring himself with a header only to be denied by a point-blank save by Arnold. He didn't have as much joy in the second-half and got himself sent off late on. Photo: Tina Jenner