Port Vale had shocked the home side when Ross Gardner netted a spectacular effort on 12 minutes, but Orient defender Matt Lockwood with his ninth of the season levelled before Jabo Ibehre netted the winner four minutes from time.
Orient had made a bright start and winger Shane Tudor was full of early menace down the right, but it was Port Vale who stunned the home side with an out of the blue goal on 12 minutes.
Poor defending cost the home side dear as Alton Thelwell's tame defensive header was seized upon by Gardner and he was given too much time and space by the home defence before he unleashed a stunning 20-yard drive into the top corner of the net.
Orient hit back but struggled to find any penetration. Striker Ibehre saw an effort pushed away for a corner by Vale keeper Joe Anyon, then Justin Miller saw a shot deflected inches wide.
Port Vale suffered a blow when recent signing Luke Rodgers suffered an injury and had to be replaced by Akpo Sodje ten minutes before the break.
But Port Vale held firm although keeper Anyon was forced into a smart save from the livewire Tudor on the stroke of half-time.
After the break Orient striker Gary Alexander was twice denied by Anyon as Orient continued to press.
The home side were finally rewarded with a leveller on 68 minutes when substitute James Walker sent Tudor scurrying down the right and his cross was met by Orient skipper Lockwood who surprised everybody by racing into the box.
Orient's tails were up and Ibehre could have added a second before Vale suffered another blow on 76 minutes when defender Jason Talbot saw red after picking up his second yellow card for a foul on Tudor.
Sodje almost put Vale back in front but was denied by Glyn Garner's smart stop before the O's snatched their second successive victory four minutes from time.
Tudor crossed again from the right and Ibehre headed home his fourth of the season.
The visitors should have snatched a point when skipper George Pilkington headed wide from close range in the fourth minute of stoppage time.