Midfielder Olli Banks headed the visitors into a 48th-minute lead and Marc Richards double their advantage in the 78th minute.
The visitors had the advantage of a strong wind in their favour in the first half, but rarely tested Exeter goalkeeper Artur Krysiak.
The one time they did was early in the game, but Tendayi Darikwa's long-range shot was pushed round the post.
Exeter's efforts were coming from distance with David Wheeler and Liam Sercombe both off target and they fell behind early in the second half when Banks rose to power in Callum McFadzean's corner.
The Grecians lost their way after that - they were poor throughout the second half - and just seconds after a double substitution, Chesterfield struck a second after a neat passing move ended with Richards waltzing through and side-footing into the corner.
Exeter gave it plenty of huff and puff after that, but were poor in the final third and managed only one effort on target throughout game.
Arron Davies missed their best chance when he dragged wide of goal from eight yards, while Chesterfield were happy to play out the game and assume pole position ahead of the weekend fixtures.