The visitors led 1-0 at half-time thanks to a Luke Rodgers strike but they were destroyed in the second half as Tamika Mkandawire, Jabo Ibehre and a penalty from Adam Boyd saw Orient record their first win in four league games.
The home side made a bright start and only some wasteful finishing stopped them taking an early lead.
In the second minute Ibehre, making his first league start of the season, saw a shot blocked and Adam Chambers, following up, saw his effort knocked away.
Leading scorer Boyd had four efforts, the best of which hit the bar after Mkandawire headed Jason Demetriou's free-kick back into the danger area.
But Port Vale looked threatening on the break as Marc Richards headed over at the far post following a cross from Rodgers and then defender Justin Miller, back at his former club, went close with a shot from distance.
Five minutes before the interval Joe Anyon's long goal kick was headed on by Richards and Rodgers shook off Mkandawire to slide home the opener.
But after the break, Orient discovered their cutting edge as Mkandawire went close and Boyd had a penalty appeal turned down.
In the 54th minute the O's finally levelled when the two central defenders combined - Brian Saah crossing from the left and Mkandawire heading home his third goal of the season.
Two minutes later Ibehre dived to head home his second goal of the campaign following an excellent right-wing cross from John Melligan.
The misery for Vale's caretaker boss Dean Glover was complete on the hour when goalkeeper Anyon felled Chambers and Boyd drilled home the spot-kick.
After that the floodgates should have opened as Paul Terry had two great chances and Charlie Daniels and Chambers also went close.