Two goals from Steve Flack a minute either side of half-time was enough to give victory to Exeter.
The home side were on top throughout the game despite falling a goal behind in the 10th minute. Stuart Green finished off a fine passing move with a low shot under the goalkeeper.
At that stage Hull were on top but Exeter fought hard to get back into the game.
They drew level midway through the half through former Manchester United winger Lee Sharpe. He curled home a magnificent 20-yard strike from the edge of the box.
Green was then given his marching orders from the referee after allegedly using an elbow against Exeter's Justin Walker.
In first-half injury time Exeter made Hull pay for their third sending off of the season.
Glenn Cronin's cross shold have been dealt with by the Hull defence but instead they allowed Flack to bundle the ball home from close range.
It took Exeter only 23 seconds after the restart to go further ahead.
Justin Walker's hit a long ball to man of the match James Coppinger and his fine cross was glanced home by Flack.
The Exeter striker came close to completing his hat-trick when he glanced another Coppinger cross just past the post.
Coppinger was unlucky not to score himself when he danced into the box and forced Matt Glennon to make an outstanding save.
At the other end former Exeter striker Gary Alexander went close with a header narrowly over the bar.
But Exeter were worthy winners and could have won the game by a much bigger margin.
Exeter boss John Cornforth said: "I thought we were outstanding today from one right through to 11. I think realistically we could have scored six and it was an outstanding performance."