The action swung from end to end during an open and entertaining start to the contest, but it was the visitors who were posing the biggest threat.
Home goalkeeper Chris Neal made two fine saves to deny Mark Randall and an even better effort to keep out a 30-yard free-kick from ex-Vale striker Marc Richards.
But increasing pressure finally paid dividends when Chesterfield debutant Jay O'Shea, on loan from MK Dons, scored in the 37th minute.
Richards played the ball into his path and O'Shea, who also had a spell on loan with Vale, took a touch before placing a low shot inside the unguarded Neal's right-hand post from 14 yards.
Chesterfield, with the impressive Randall running the show, continued to dominate after the break as the midfielder, with an audacious 45-yard effort, Boa Morte and Richards forced further saves from Neal.
But the Vale keeper was left stranded in the 64th minute when Richards' cross from the left was deflected to the far post where Tendayi Darikwa headed into an empty net from two yards.
Prolific marksman Tom Pope forced two decent saves from the previously redundant Tommy Lee, but a Vale comeback never looked likely.