Scott Arfield and Jordan Rhodes grabbed the goals for Town either side of half-time at Brisbane Road, with Dean Cox's strike little more than a consolation for the hosts.
The Terriers went ahead in the third minute, Scott Arfield hammering a shot into the top corner after Orient had failed to clear a free-kick.
Orient went close after the interval when Alex Smithies turned over a fierce drive from Scott McGleish.
But it was Huddersfield who scored the second goal of the game with 12 minutes remaining as Jordan Rhodes fired past Jamie Jones with the aid of a deflection.
Cox's powerful 25-yarder then set up a grandstand finish, which saw Huddersfield's Jamie McCombe strike the bar before Orient's James Walker had a shot cleared off the line by Peter Clarke.