Scot Bennett netted in between John O'Flynn's double as the Grecians climbed up to third place in the table.
The Shrimpers thought they had scored when Barry Corr's header hit the underside of the crossbar, but despite their appeals for a goal referee Roger East waved play on.
The deadlock was broken two minutes before half-time. Bennett and Matt Oakley did well in midfield to feed Alan Gow and he slipped the ball wide to O'Flynn.
The Irish striker took one touch before lashing a low shot across the face of goal that flew past goalkeeper Paul Smith and went in off the far post.
Gavin Tomlin shot over the bar as Southend rallied at the start of the second half but Exeter, with only three wins at home all season before this game, doubled their lead with 10 minutes remaining.
Oakley's corner was aimed for the far post where the back-pedalling Bennett headed back across goal and inside the far post.
With Southend all at sea, O'Flynn wrapped up the points with a simple tap-in after a brilliant run by Jimmy Keohane.