Colchester took the lead midway through the half, as Tariq Fosu headed in from close range.
The O’s equalised early in the second half, with a superb individual strike from Sandro Semedo.
The visitors restored their advantage late in the match, as captain Chris Porter tapped in from close range and the game was wrapped up with a third minutes later through substitute Macauley Bonne.
The match was then stopped after Orient supporters invaded the pitch and the final minutes were finished behind closed doors.
Omer Riza made three changes to the O’s side that were relegated after a 3-0 away defeat to Crewe Alexandra last weekend, as Callum Kennedy, Paul McCallum and Jense Jans start ahead of Teddy Mezague, Henry Ochieng and Victor Adeboyejo who shift to the bench.
Colchester had the opening oppertunity, as George Elokobi’s cross field ball to Richard Brindley was cut back to Tom Eastman whose shot was blocked by Aron Pollock.
From the resulting corner, Sean Murray’s whipped in ball was met by Elokobi but his header was weak and straight into the hands of Sam Sargeant.
Orient made their first threat on goal, through Steven Alzate as he threaded the ball into Tristan Abrahams on the edge of the box and hit his shot on the turn which trickled wide of the target.
Colchester then had a dangerous free-kick 25 minutes in, as Brindley whipped in ball fizzed just over the Orient bar.
The visitors’ then grabbed the opener shortly after, as Eastman’s cross was met by Fosu at the far past who guided it past Sargeant.
Orient nearly responded, as Abrahams turned on the edge of the box and curled his shot which went just over the bar.
Just before the break Orient had their best chance of the half, as Kennedy’s early cross for McCallum was stopped by Sam Walker.
In the second half, Orient responded seven minutes into the half as Semedo burst forward and hit a rocket of a strike from Semedo for the equaliser.
Colchester almost restored their lead as Matt Briggs’ hit on the half volley deflected off the Orient defender and looped just over the bar.
Fosu again caused the O’s problems, as he went passed three Orient defenders inside the box but his shot from close range was tame and straight at Sargeant.
Colchester then regained the lead from poor defending by Orient, as Pollock’s pass back was short to Sargeant and Fosu ran on to the loose ball went around Sargeant and cut it back for Porter to tap into an empty net.
The visitors then extended their advamtage, as substitue Bonne wrapped it up with a shot which found the far bottom corner.
The game was then stopped with less than ten minutes remaining after Orient supporters invaded the pitch.
the game restarted two hours after the invasion behind closed doors where the match peated out as Freddie Moncur replaced Micheal Collins.
Leyton Orient Lineup: 24 Sam Sargeant, 3 Callum Kennedy, 6 Tom Parkes, 7 Michael Collins (C), 10 Paul McCallum (67), 22 Sandro Semedo, 25 Aron Pollock, 31 Steven Alzate, 34 Michael Clark, 35 Tristan Abrahams, 46 Jens Janse (79)
Substitutes: 39 Arthur Janata, 18 Ulrich Nnomo, 19 Teddy Mezague, 23 Teddy Moncur, 26 Victor Adeboyejo (67), 28 Josh Koroma (79), 32 Henry Ochieng
Colchester United Lineup: 1 Sam Walker, 2 Richard Brindley, 3 Matt Briggs (70), 4 Tom Lapslie, 7 Drey Wirght, 9 Chris Porter (C), 14 Alex Wynter, 15 George Elokobi, 18 Tom Eastman, 23 Sean Murray (74), 31 Tariq Fosu
Substitutes: 29 Dean Brill, 8 Doug Loft (74), 12 Kane Vincent-Young, 19 Macauley Bonne (70), 27 Rekeil Pyke, 32 Tommy O’Sullivan, 33 Lewis Kinsella
Attendance: 6,854 (1,257)
Jay Simpson opened the scoring with a tidy finish early in the first half for his first goal of the season.
Nicky Hunt struck the O’s second in the opening minutes of the second half, which then spurred a superb Simpson strike from long range to cap of the convincing victory for Orient, as they move up to 19th in the table.
Alberto Cavasin made seven changes to his that were hit for six in the FA Cup last weekend by Sheffield United. Whereas Colchester defender Luke Prosser was injured in the warm-up and was replaced by Frankie Kent.
Leyton Orient took the lead just 11 minutes in with the first real attack of the match, as the ball was not cleared by Colchester. A fortunate ricochet off the Colchester defender for Orient inside the box put Simpson in on goal to tuck it passed Sam Walker.
Orient were the more threatening, as a long ball was headed down by Simpson for former U’s winger Gavin Massey to hit on the volley but was well stopped by Walker.
Colchester were struggling to break Orient down, as Richard Brindley had a shot from 30 yards which went well wide of the target.
Massey burst down the left and into the box but his ball across goal could not be turned in by Simpson as it went all the way across the Colchester box.
The hosts pressed before the break for the equaliser, as Drey Wright’s shot was straight at Alex Cisak.
Brennan Dickenson for Colchester whipped in a dangerous ball in injury time to the far post but could not be turned in despite the home sides on rushing sliding efforts.
In the second half, Orient scored virtually from the restart after Collins’ endeavour to keep the ball in out wide was rewarded, as the ball fell to Hunt whose drive went low into the bottom corner.
The hosts had a glorious chance to get back into the game, as Dickenson cut the ball back across goal for Kurtis Guthrie to have a shot unmarked inside the box but dragged it wide.
Just after the hour mark, Dickenson was again dangerous down the left as he hit a fierce shot which stung the hands of Cisak but was cleared by the Orient defence.
Colchester possession dominance showed over Orient, as Tom Lapslie found some space on the edge of the box but his shot went over the bar.
Just when Colchester looked like getting back into the match, a long ball by Cisak was headed by Ollie Palmer into the path of Simpson who strike from 20 yards went straight into the top left corner, to secure the three points for Orient.
Orient were then playing with confidence, as Callum Kennedy clipped the ball into Palmer who headed the ball into the path of Massey whose volley was saved by Walker.
Captain Robbie Weir then got in on the action, as he drove in a shot from a broken down corner to lash his shot goalwards, which was tipped over the bar superbly by Walker.
Leyton Orient secured their fourth away victory of the season, as they jump ahead of Colchester and look to carry the confidence into their game at home against Blackpool next weekend.
Colchester United Lineup: 1Sam Walker, 2 Richard Brindley (68), 4 Tom Lapslie, Frankie Kent, 7 Drey Wright, 11 Brennan Dickenson, 14 Alex Wynter, 18 Tom Eastman, 19 Macauley Bonne, 28 Kurtis Guthrie (54), 32 Glen Kamara (54)
Substitutes: 25 Dillon Barnes, 10 Sammie Szmodics, 17 Denny Johnstone (54), 24 Craig Slater (54), 31 Tarique Fosu (68), 41 Louis Dunne
Leyton Orient Lineup: 1 Alex Cisak, 3 Callum Kennedy, 6 Tom Parkes, 7 Michael Collins, 8 Robbie Weir, 9 Ollie Palmer (90), 11 Gavin Massey (78), 15 Nigel Atangana, 16 Nicky Hunt, 27 Jay Simpson (84), 37 Yvan Erichot
Substitutes: 24 Sam Sargeant, 5 Alan Dunne, 10 Paul McCallum (84), 22 Sandro Semedo (78), 25 Aron Pollock, 26 Victor Adeboyejo (90), 32 Henry Ochieng