The hosts took just 47 seconds to take the lead, which came after Kevin Betsy's cross from the right byline was not cleared by the Orient defence and Lee Barnard shot the ball home from six yards out.
And the Shrimpers doubled their advantage in the 12th minute when Dan Harding crossed from the left and Dougie Freedman headed to Lee Sawyer, who lashed the ball past Glenn Morris from six yards.
Southend continued to look the sharper side in the first half and saw Morris save a Sawyer header and Barnard screw a 12-yard effort wide of the right post.
Betsy then squared to Freedman whose shot from 18 yards was palmed out for a corner by Morris.
Orient's chances were few and far between, with Ryan Jarvis heading wide from six yards before John Melligan and Paul Terry saw shots from distance easily held by debutant keeper Adam Federici, who is on a month's loan from Reading.
Martin Ling brought on Andre Cave-Brown and Dean Morgan at the start of the second half and that, along with his half-time pep talk, saw Orient begin to dominate.
Jarvis mis-hit a shot way off target when well placed and Morgan's effort from 20 yards was saved by Federici.
Southend saw Hal Robson-Kanu fire wide before the midfielder set up the third goal on 70 minutes. His cross from the right evaded Barnard, but Freedman was at the far post to score.
Barnard then dispossessed Morris but saw his effort from a tight angle cleared to safety.