First-half goals by Fulham loanee Cauley Woodrow and Kevan Hurst were enough for the Shrimpers as they inflicted a third successive league defeat on their promotion rivals.
Southend looked by far the better team in the first half and went in front after 12 minutes. Hurst crossed low from the right and Woodrow nipped ahead of his marker to pip goalkeeper Artur Krysiak to the ball and divert it over the line.
Exeter had chances through 17-year-old debutant Matt Jay, who was one of the few positives for the hosts, and Liam Sercombe, but Jay lacked power and Sercombe's effort was wild.
And Southend duly doubled their lead after 29 minutes. Again, it was a cross which Exeter failed to deal with and as the ball dropped from high, Hurst put his foot through it from 15 yards.
Exeter improved after the break but failed to test goalkeeper Daniel Bentley as the visitors held on comfortably for the three points.