It all looked to be going in the other direction when Keigan Parker put the home side, who last won on the first day of the season in 2000, 1-0 after five minutes.
The opening minutes gave some indication of the topsy-turvy 90 minutes to come with Chesterfield's Aaron Downes heading against the crossbar before Parker's breakthrough.
The goal came when Chesterfield only half cleared a left-wing corner from debutant Rory Prendergast and Parker hit a fine half-volley which beat keeper Barry Roche at his far post.
Blackpool looked the stronger side early on but Chesterfield hit back after 23 minutes.
Blackpool debutant John Doolan lost possession in the midfield and impressive young winger Adam Smith ran at the heart of the defence before sliding a pass to veteran striker Wayne Allison who saw his first attempt saved by Lee Jones but tapped home the rebound.
Blackpool almost hit back immediately when Prendergast again got down the left wing and put in a great cross for another debut boy, Scott Vernon, who hit his shot just wide of Roche's post.
Worse was to come for Blackpool on 39 minutes as again Smith was their tormenter, cutting inside and out before crossing for the unmarked Mark De Bolla to head past the helpless Jones.
Blackpool reorganised and attempted to hit back after the break but created few chances and eventually it was Chesterfield who added a third when a straightforward long ball into the box was easily headed home by veteran defender Steve Blatherwick.