Jay Simpson had given the O’s the lead early on with an eighth minute strike, but his opener was cancelled out by Roarie Deacon midway inside the first half.
Mitch Hancox then put Crawley ahead with a strike from outside the box on the 37th minute before Alan Dunne was sent off on the stroke of half time and Simon Walton converted a third from the ensuing penalty.
Simpson then added his second on the 81st minute but it was not to be enough as it proved to be too little, too late for the O's.
After returning to winning ways last weekend at home to Notts County, Ian Hendon was forced into making one change to the starting XI.
Captain Mathieu Baudry was ruled out with a head injury which saw Alan Dunne partner Connor Essam, who was coming up against one of his former sides, in the centre of defence.
The O’s were yet to record a victory in any of their previous trips to Crawley but despite this, it was the East Londoners who started the brighter.
Dean Cox came close with a free-kick inside the opening four minutes but soon after Orient made the breakthrough with Bradley Pritchard at the heart of the attack.
The Zimbabwean picked up the ball in the middle of the park before bursting towards the Crawley defence.
With options either side, Pritchard then picked out Chicksen to his left who then crossed towards Ollie Palmer who saw his effort kept out by Reds goalkeeper Callum Preston, but Jay Simpson was well positioned to stroke home his eighth of the season.
Pritchard was proving to be a real handful for the hosts and the midfielder came close twice before Simpson should really have doubled his tally for the afternoon.
The O’s top scorer managed to beat the offside trap to reach Palmer’s through ball only to waste the chance as his could only lift an effort over Preston which dropped narrowly wide.
Despite Orient having enjoyed all of the early exchanges the hosts made the most of their first attack to equalise.
A free-kick from deep inside the Crawley half was launched forward by Preston and it was flicked on into the path of Roarie Deacon who precisely rolled an effort in off the bottom far post.
Before the goal it had been all Orient but ten minutes later, Crawley took the lead when Mitch Hancox caught out Alex Cisak with a curling shot that creeped in at the near post from the corner of the box.
As half-time beckoned Orient were then left with a real uphill struggle as the hosts were awarded a penalty and Alan Dunne was given his marching orders for bringing down Rhys Murphy as the striker honed in on goal.
Simon Walton stepped up to take the spot-kick and made no mistake as he sent Cisak the wrong way by going low to his right in what was the final action of the half.
In response to the sending-off Orient made one change at the break as John Marquis replaced Palmer to make his debut, while Pritchard dropped back from midfield to take up the right-back position with Sean Clohessy moving into centre half.
The makeshift backline were then tested just shy of the hour as Matt Harrold got up well to direct a header towards the bottom corner only for Cisak to get down well and parry the ball away.
Marquis then nearly grabbed himself a debut goal two minutes later as he connected well with a Pritchard cross but his header was expertly kept out by the foot of Preston.
With an hour played O’s Hendon then shuffled the team once again as he introduced Blair Turgott in place of Cox and changed to a 3-4-2 formation.
Sammy Moore then came close to repeating his goalscoring heroics from the previous weekend after being teed up by Pritchard but Preston was on hand once again to tip his effort over the bar.
With nine minutes remaining the O's pulled a goal back as Marquis showed good work down the right and pulled it back for Simpson to sweep home his second and set up a tense ending to the match.
As the O's desperataly searched for an equaliser a long throw into the box from Jack Payne caused a scramble in the penalty area but Moore's shot failed to find its way beyond a crowd of bodies and was eventually cleared.
Six minutes stoppage time was then shown by the fourth official but despite the best efforts of Orient, Crawley managed to hold on for all three points and secure their first home victory of the season.
CRAWLEY: Preston, Young, Bradley (C), McNerney (Ashton 63), Hancox, Edwards, Smith, Walton, Deacon (Tomlin 68), Harrold, Murphy (Fenelon 82)
SUBS: Scales, Barnard, Rooney, Jenkins
GOALS: Deacon (27), Hancox (37), Walton (45 pen)
BOOKINGS: Deacon (51), Tomlin (90+6)
ORIENT: Cisak, Clohessy (C), Dunne, Essam, Chicksen, Payne (Kashket 87), Pritchard, Moore, Cox (Turgott 60), Palmer (Marquis HT), Simpson
SUBS: Grainger, Shaw, James, Moncur
GOALS: Simpson (8 & 81)
SENT OFF: Dunne (45)
REFEREE: Kevin Wright
ATTENDANCE: 2,515 (826 Orient fans) Read more at http://www.leytonorient.com/news/article/crawley-town-v-leyton-orient-match-report-2737478.aspx#Hq1GJiIquEw1Xfyx.99