Orient opened the scoring with top scorer Scott McGleish's 18th goal of the season. McGleish sent recalled Argyle goalkeeper Romain Larrieu the wrong way from the penalty spot after 13 minutes after Matt Spring's goal-bound drive was handled by teenage defender Curtis Nelson.
Plymouth were reeling seconds later as Dean Cox got up from a foul by home skipper Carl Fletcher and swung in a free-kick from 20 yards to make it 2-0 to Orient with just 15 minutes on the clock.
After 63 minutes Yannick Bolasie let fly with a thumping right-foot shot on the run from 25 yards that flew in to make it 2-1.
Home keeper Larrieu was sent off for handling outside his area to deny Alex Revell as he pounced on Nelson's poor back header. Revell scored from the subsequent 77th minute free-kick, with the aid of a deflection to beat substitute keeper David Button.
Substitute Revell completed the rout by converting Charlie Daniels' left wing cross in the 89th minute.