Home skipper Antony Kay was left completely unmarked as he headed in a Charlie Barnett corner after only six minutes.
But Huddersfield drew level after 23 minutes with a fine header by Andy Booth from Michael Collins' cross after patient build-up play.
The goals apart there were precious few chances in the opening 45 minutes.
Tranmere took command with two goals at the start of the second half. Bas Savage scored with a terrific strike from the corner of the box after 50 minutes.
And Kay made it 11 goals for the season with a neat finish from 12 yards after an Andy Taylor free-kick was not cleared.