The visitors survived an early second-half battering to snatch the points when Josh Wright’s first goal for Orient won it with 12 minutes left.
Victory lifted them out of the relegation zone and two points clear of the bottom four.
The Sky Blues have won just once in the league at the Ricoh Arena in the last five months and, despite dominating for long spells, failed to shake their home hoodoo.
Grant Ward hit a post, Conor Thomas had a shot cleared off the line and Jim O’Brien went close but they remain three points above the danger zone.
Orient, without David Mooney who was sidelined with a rib injury, started the game four points behind the Sky Blues and the hosts looked for the kill early.
O’Brien flashed a drive over after three minutes while Ward’s 16th-minute free-kick was just off target.
But a scrappy game had little flow until it sprung into life after 28 minutes.
First, Mathieu Baudry saw a header deflect just wide before Coventry almost grabbed the lead five minutes before the break.
Frank Nouble tricked his way to the byline and crossed for O’Brien but the midfielder’s effort dropped a yard wide of the far post.
But Orient blew their best chance in first-half injury time when Chris Dagnall latched onto Darius Henderson’s flick only for Lee Burge to claw away his six-yard header.
The striker, who was on loan at the Ricoh last season, was wasteful and Orient almost paid the price two minutes after the re-start.
Ward played a quick short corner and wriggled away on the left before curling a brilliant effort against the post.
The Sky Blues were on top and four minutes later Baudry rescued Alex Cisak with a goalline clearance after the keeper’s punch hit Thomas and allowed him to shoot.
Orient offered little with Coventry dominating but the hosts failed to find a way through the visitors’ defence.
And without a goal Sky Blues’ momentum evaporated and Orient stunned the hosts with the winner on 78 minutes.
A clever break found Dagnall and his cute pass picked out the overlapping Wright to bury past Burge at the near post from seven yards.