Three goals in 14 devastating second-half minutes from Josh Koroma, Matty Pearson and Jonathan Hogg stunned the hosts, as the Terriers completed a fourth victory in five matches.
Blackpool, who were arguably the better side in the first half, slipped back into the drop zone after they had secured a first win of the season at the weekend.
There was a superb atmosphere inside Bloomfield Road for this Roses clash, but the game itself took a while to light up.
It was Blackpool who had the first chance after eight minutes, but Luke Garbutt fluffed his free-kick attempt from 22 yards.
It was the 20th minute before the next opportunity came, and again it was the hosts who threatened.
This time Garbutt floated in a free-kick from the left for Kenny Dougall, but he headed wide of the far post.
Carlos Corberan's Terriers had scarcely been a threat in the opening quarter, and they ought to have done better when Harry Toffolo nodded Sorba Thomas' hanging cross off target.
Clearly buoyed by Saturday's maiden win of the campaign against pace-setters Fulham, Blackpool appeared determined to back that result up and a brilliant save from Lee Nicholls thwarted them just past the half-hour mark.
Garbutt's corner drifted out to Dougall 15 yards from goal and his piledriver was superbly beaten away by the Huddersfield keeper.
Eight minutes before the break, the hosts went close again when Shayne Lavery met Garbutt's corner at the near post, only to head into the side-netting.
Few would disagree that the Seasiders had enjoyed much the better of the opening 45 minutes, but there had been no reward for either side.
The last action of the first period saw Huddersfield's Danel Sinani see a well-hit strike deflected narrowly wide.
The visitors broke the deadlock in some style three minutes after the restart.
Koroma did the business, steadying and cracking home from the edge of the box after meeting Lewis O'Brien's short pass.
Blackpool almost replied swiftly when Lavery headed onto the roof of the net, but it was the visitors who had flown out of the blocks in the second period.
Huddersfield's lead was doubled in the 54th minute.
Sinani whipped in a vicious inswinging corner which was bundled home at the near post by centre-back Pearson.
Just past the hour mark the Terriers extended their lead. Skipper Hogg made it three, firing home a clinical half-volley after Blackpool keeper Chris Maxwell could only parry Koroma's initial strike.
With victory now secured, Huddersfield coasted through the remainder of the game as Blackpool's weekend match-winner Josh Bowler curled a late effort inches off target.