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...
1. Melvin Minter 7
A mixed afternoon. He was a bit shaky when coming for set-pieces and corners but he was much-improved in that regard in the second-half. He made two good saves after the break, the second was a top stop down to his left to deny Murphy one-on-one. Gave away a penalty in injury-time when he bundled over Rush in the area. Photo: Jason Chadwick
2. Fraser Kerr 6
He was out of position for Southend's goal and there were a couple of similar situations where he was caught napping. He has been excellent in recent weeks but this was an off-day by his high standards. He was playing in a makeshift defence so we can forgive him. Photo: Tina Jenner
3. Luke Croll 8
My man of the match. Considering he was only announced as a Spireites player at lunchtime, he deserves a lot of credit. He played in the middle of the back three and he was calm in possession and played some nice passes. He grew into the game defensively and mopped up well at the back in the second-half. He scored 14 minutes into his debut to make it 2-1, swivelling in the box to finish with the help of the post. Photo: Warren Little
4. Alex Whittle 8
Slightly just edged out by Croll for my man of the match but he was superb. Playing out of posiiton on the left of the three-man defence, he bombed forward to create overlaps with Miller down the left and had a lot of success. Going the other way, he covered for Kerr and Croll well at times. In general it was a whole-hearted performance. He has been given his chance due to the injury situation and he is taking it so far. Photo: Tina Jenner