The visitors claimed victory courtesy of a scrappy 72nd minute Gary McSheffrey winner while home defender Ritchie Sutton was stretchered off with what looked a serious injury after a 12-minute halt.
Sutton was hurt in a collision with his keeper Alan Marriott as both went for a high Sam Hird cross from the right, which allowed the ball to run loose to McSheffrey to find the empty net from 12 yards.
It was sweet revenge for Stags' 1-0 League Two win at the Proact Stadium 10 days earlier.
In an all-action first half, Mansfield carved out the best chances and Lee Stevenson should have put them ahead after eight minutes when put clean through by Sam Clucas only to see Tommy Lee make the save.
Chesterfield had not troubled Marriott much in the home goal. But right on half-time he had to stretch high to his left to turn away Jamie Devitt's goalbound 25-yard free-kick.
However, the second half was a different story as the visitors raised a gear and Chris Porter twice came close in the opening 11 minutes, seeing one finish come off his shins wide from four yards and guiding an eight-yard header wide from Jimmy Ryan's cross.
Jay O'Shea then brought another good stop out of Marriott.
Stags rallied and Stevenson sent Junior Daniel through one one after 64 minutes only to see Lee again make the block.
The pendulum then swung firmly to Chesterfield after 72 minutes as McSheffrey struck.
Keeper Lee was again the hero right at the death as he tipped over a superb effort from sub Ollie Palmer.