Southend United made it two wins from two in the Checkatrade Trophy which ensures progression to the next stage of the competition.
Marc-Antoine Fortune produced the game's only goal with a wonderfully taken effort ten minutes from time.
And the three points, on top of that from the win over Brighton & Hove Albion, means Blues move clear at the top of Southern Group G on six points.
Phil Brown made six changes from the Sky Bet League One draw with Peterborough on Saturday, including a first start for new signing Marc-Antoine Fortune alongside Simon Cox in attack.
It was a very quiet start to the game and it took until the eleventh minute for either side to get a sight at goal. Gavin Massey's speculative strike from 25 yards for the visitor's was no where near troubling Mark Oxley though.
Orient looked to threaten again from a set-piece which came to nothing before Luke O'Neill got Blues' first real chance which he flashed wide of the right post from 20 yards.
Blues began to find their straps from that moment on, despite failing to create many clear cut chances.
From the right wing, Fortune tried to pick out his strike partner, Cox, in the box, but Orient cleared.
Ryan Inniss then rose highest to connect with an in-swinging free-kick, but his header was comfortably saved by Sam Sargeant.
Undoubtedly the best chance of the half came five minutes before half time, but Ryan Leonard failed to make Sargeant pay for parrying Cox's initial 20 yard shot straight to him by volleying the rebound wide from five yards.
Right on half time Cox fired over from Wordsworth's corner, bringing the half to a close with nothing separating the sides.
Half time: Southend 0-0 Leyton Orient
Orient made two changes at the break, Jens Janse for Gavin Massey and Alan Dunne for Tom Parkes, whom both immediately made a difference for Alberto Cavasin's side.
Ulrich Nnomo headed a great chance inches over five minutes into the half before the sub Janse squared the ball to Jordan Bowery who made Oxley dive to his left and produce a great stop.
Brown looked to his bench on the hour mark to try and find the breakthrough with Anthony Wordsworth and Adam King making way for Will Atkinson and Stephen McLaughlin.
Nnomo had another attempted header, this time at the back post, which was headed wide, despite some Orient fans thinking it had nestled the other side of the post.
Fortune came within inches of opening his account for Blues but O'Neill's cross just evaded him.
Moments later Coker's cross was drilled in with pace, but failed to find a Blue shirt as Orient cleared for a corner.
Brown, watching from the stands, made his final substitution on the 80th minute in the way of Jack Bridge for O'Neill.
And seconds later, Fortune did have his first Southend goal. Cox played it forward to his strike partner who had time to turn and curl his shot in off the post.
Blues saw the game out from there with ease to take some good form into the trip to Rochdale.
SOUTHEND XI | Oxley, White, Inniss, Thompson, Coker, O'Neill, King, Leonard, Wordsworth, Cox, Fortune.
SUBS | Smith, Sokolik, Kyprianou, Atkinson, Bridge, McLaughlin, Mooney.
LEYTON ORIENT XI | Sargeant, Kennedy, Kelly, Parkes, Weir, Palmer, Massey, Hunt, Nnomo, Bowery, Pollock.
SUBS | Clark, Dunne, Simpson, Koroma, Alzate, Benedicic, Janse.
Attendance | 2,383 (413 away)