At half time the Spireites were leading Sheffield United after a strong 45 minutes, but after the break it was all Blades with the hosts unable to cope, falling to a 4-1 loss.
Jon Nolan had given Chesterfield the perfect start with a rasping goal after 90 seconds, but after the break the Blades fought back with strikes from Kieron Freeman, John Fleck, Billy Sharp and Leon Clarke sealing the home side's fate.
"The first half was excellent," explained manager Danny Wilson. "I thought we played very well and dominated large parts of it. We played some good football, had some good opportunities and came in at 1-0 when it could possibly have been 2-0, which would have been terrific.
"Everything was going well, we passed the ball well, took the ball away from them and our counter-attack football was excellent.
"Second half and we conceded a goal, a soft goal. Still we had chances, we had a great chance to make it 2-1 after that but for a great save by Simon Moore - anyone following up would have had an empty net to score into.
"You see them then, what a good side they are with their tails up and with quality going forwards - possibly a lot more than we have. Overall they came out strong winners."
A key passage of play took part in the middle of the second half when both Ched Evans and Jon Nolan needing substituting with injuries, and not long later United took a stranglehold of the game.
"Losing the two boys knocked our rhythm," said the manager. "We won't know their injuries until tomorrow but it's a hamstring (Nolan) and an ankle (Evans) injury.
"I don't think any team can afford to lose their better players. We can't afford to lose two more players on top of what we've already lost, it's a blow but we have to get on with it."