They dominated in the opening period and built up a two-goal advantage. Huddersfield rallied well after the break but rarely tested home keeper John Achterberg before Rovers wrapped it up with their third strike in injury-time.
Eugene Dadi gave Tranmere a 16th minute breakthrough with a close-range effort after good work by Iain Hume and Ian Goodison.
Hume doubled the lead in the 24th minute with an excellent angled shot following a headed pass from Ian Sharps. It was his 13th league goal of the campaign.
Paul Hall had a goal disallowed for a marginal offside decision in the 29th minute and Gareth Roberts and Hall wasted gilt-edged chances before the break.
Town keeper Paul Rachubka did well to tip over a Hume effort after 49 minutes before Roberts missed the target with an easy chance two minutes later.
Danny Schofield finally tested Achterberg before Jon Worthington saw a good strike deflected over.
Hume missed a great chance in the 90th minute when Rachubka blocked his shot, but the Canadian provided the cross-field pass for Roberts to make it 3-0 with an angled strike deep into injury-time.