It was the first time the Blues had lost on home turf this year and marked the O's first win away from Brisbane Road since November.
Matches between the two sides are always fiercely contested, so it came as no surprise that the game started at a frantic pace, with Freddy Eastwood having the opening chance of the game.
But it was Orient who made their presence felt when Daryl McMahon hit the crossbar with a 25-yard effort on 15 minutes.
Southend were left ruing a wasted Adam Barrett opening when Matt Lockwood's corner from the right was headed in at the far post by John Mackie after 22 minutes.
The Shrimpers saw another Lockwood flag-kick headed wide by Gaby Zakauni minutes later before Lockwood's free-kick from the right was headed against the left upright after 32 minutes.
Southend upped the tempo after the break as their visitors put men behind the ball.
But the Shrimpers struggled to create real chances until Orient goalkeeper Lee Harrison was forced into action to deny Wayne Gray and then block a Mark Bentley shot following a strong run.
Home fans were left screaming their disapproval on the hour mark after Gray's run on goal was stopped by a Mackie foul that went unpunished by referee Phil Dowd.
Their frustrations continued to rise as Harrison foiled Eastwood and Mark Gower, while other shots went astray.
Orient were quite happy defending their lead and trying to catch Southend on the break.
And they should have made it 2-0 after 63 minutes when Lee Steele crossed from the byline to strike partner Gary Alexander, whose point-blank header was blocked by Darryl Flahavan.