A goal in the first minute of the second half from striker Roy Essandoh was enough to give Gravesend a surprise victory at St James' Park.
The visitors were good value for the three points and were the better side throughout.
Exeter pressed and probed but it was a poor performance from one of the Conference's fancied sides.
Apart from a short spell after they had fallen a goal behind, Exeter never looked threatening.
Gravesend looked far more positive and a rare clean sheet meant they held on for a deserved win despite late pressure from the Grecians.
Steve Perkins thumped a long-range shot past the post in the first minute as Gravesend started brightly.
Exeter's best early moment came when James Coppinger curled a free kick into the arms of the goalkeeper.
Sean Devine should have put the Grecians ahead in the tenth minute. Alex Jeannin's deep cross was fumbled by the goalkeeper but Devine could only shoot wide from four yards.
Ben Abbey controlled the ball on the edge of the box for Gravesend and his attempt to lob the goalkeeper came back off the top of the crossbar.
Lee Protheroe then struck a long-range shot at James Bittner as the visitors began to dominate.
Gravesend were ahead just 41 seconds after the restart. There looked little danger as Abbey found Essandoh 40 yards from goal but the striker just kept running, skipping past two defenders before slotting the ball superbly past Bittner.
The goal finally stirred City into action and Coppinger's fine cross was headed against the crossbar by Steve Flack.
Devine then stroked a ball across the face of goal and found Gareth Sheldon, who fired over the bar from a tight angle.
In the dying minutes substitute Dean Moxey thumped the ball over the bar from close range following Sheldon's long throw But it was too little too late for Exeter.