Bristol Rovers gave their Football League survival hopes a massive boost as goals from Giuliano Grazioli and Paul Tait saw them stretch their unbeaten run to seven games.
But the defeat means that Orient have not won at home in their last six matches and could be yet dragged in to the relegation battle.
But victory was no more than Rovers deserved as they started well and carved out three good early openings.
Grazioli and Wayne Carlisle had shots saved by Orient's debut keeper Lee Harrison and it came as no surprise when Rovers took the lead on 13 minutes.
Sonny Parker's long throw was touched down by Tait and Grazioli spun in the box and fired past Harrison from close range.
O's netted an undeserved leveller five minutes before the break when Parker was adjudged to have pushed Chris Tate as they both went for Carl Hutchings' cross.
Former Rovers player Matt Lockwood fired home the penalty into the corner of the net past Scott Howie's outstretched right hand.
Orient looked better in the second half but rarely found a way through the Rovers defence where ex-Orient players Adam Barrett and Kevin Austin were superb.
Rovers continued to create the cleaner chances. Tait shot weakly at Harrison before Grazioli skimmed the bar with a shot from a tight angle.
A minute later Tait headed home the winner from a corner by substitute Vitalijs Astafjevs, although Orient claimed defender Matthew Joseph had headed the ball away before it crossed the line.
A frustrated Orient boss Paul Brush admitted afterwards: "Our players said the ball hadn't gone over the line but let's be fair Rovers had the better chances.
"It was a disappointing result and a disappointing performance. We are not playing well enough and we're not battling well enough," he fumed.
But a delighted Pirates manager Ray Graydon said: "This was a great win for us and will give us a terrific lift. I've really enjoyed this trip to the East End."