Leeds have never lost a first round tie in the League Cup, while the Spireites have now fallen at the first hurdle in the last seven seasons. Yet it was the League Two side who seized a shock 18th-minute lead.
Tendayi Darikwa created space on the right for skipper Drew Talbot whose measured cross to the far post was headed firmly by striker Eoin Doyle past Leeds goalkeeper Paddy Kenny, who was making his 600th career appearance.
Leeds restored their pride with two goals in four minutes. First Michael Brown's 28th-minute blast from 20 yards brought the midfielder his first goal since November.
Then Ryan Edwards lost out to Dominic Poleon who advanced to the 18-yard box before shooting into the bottom left corner.
Darikwa should have restored parity but delayed his shot just long enough for Jason Pearce to clear off the line.
Everton, Southampton and Tottenham were beaten by Leeds in cup competitions at Elland Road last season but Chesterfield were far from overawed, with Gary Roberts doing the prompting.
An angry Roberts felt he should have had a 50th-minute penalty when brought down by Zac Thompson but referee Carl Boyeson ruled the offence was outside the box.
Visiting goalkeeper Tommy Lee pulled off a full-length save to deny Luke Murphy a second goal in as many games for Leeds, before Nathan Smith struck an upright for Chesterfield in added time.