The win was a huge boost to the Grecians' survival hopes and put a dent in the automatic promotion aspirations of Graham Alexander's side, who were well beaten.
Exeter dominated the first half and went in at the break in front when Danny Butterfield won his side a free-kick on the edge of the penalty box and curled a lovely ball to the back post, where Fleetwood striker Jon Parkin turned the ball past his own goalkeeper Chris Maxwel.
Exeter almost doubled their lead after a lovely passing move, but Maxwell produced an equally excellent save to deny Tom Nichols.
Nichols' persistence led to Exeter's second goal - Eliot Richards heading in at the back post from Danny Coles' flick on.
The home side underlined their victory when on-loan striker Richards bagged his second three minutes later when he reacted quickest to score after Maxwell had spilled Nichol's fierce free-kick.