Goals in either half from the visitors brought Southampton’s defence of the trophy to an end in the last 16 of the competition against the Yorkshire side.
Jack Senior’s 22nd minute strike put the Terriers ahead – a goal which owed much to the endeavour from fellow full-back Jacob Hanson, with another defender, Danny Kane, completing the job - and stretching Saints’ winless run to four games - just before the hour mark with a close range header.
This was Huddersfield’s 16th successive match without defeat and they now face Charlton Athletic in the quarter-finals of the competition.
Saints got the game under way attacking the Northam end at the scene of their cup final win last season.
The visitors in their changed strip of lime green were the brighter of the two teams from the start of the game in terms of opportunities created, but it was keenly contested battle for the opening 20 minutes or so.
Josh Debayo put a well-timed challenge on Ronan Coughlan to stop the midfielder from registering the first shot on target in the contest, but Saints had no answer to the effort from the Terries in the 22nd minute.
A surging run forward from right back Jacob Hanson caught the hosts cold, and while the ball ran loose as his break forward fizzled out, the ball ran kindly to the other full-back, Jack Senior who crashed a high shot past Paulo Gazzaniga to make it 0-1.
Buoyed by their goal Huddersfield stepped up their intentions and saw striker Duane Holmes blaze a shot over the crossbar after a good run forward, before the same man then struck the woodwork with a low shot after running onto Senior cross.
The crossbar was still rattling when Jake Charles then ventured forward to try and get the better of Gazzaniga whom he partially rounded before shooting into the side netting.
The Saints ‘keeper was called into action to push Will Boyle’s header away from a corner, before Martin Hunter’s men had their first clear opportunity at the other end just before half-time when skipper Dominic Gape struck a shot straight at Terriers ‘keeper Lloyd Allinson following a loose clearance inside the area.
Despite a flicker of resurgence from the hosts, they couldn’t get back on level terms at the start of the second half. They had one good opportunity when the ball landed at Bevis Mugabi’s feet from a corner, but the right back couldn’t place a shot on target from close range.
Alfie Jones put in a good challenge on Coughlan as the Terriers’ number seven tried to twist and turn his way through on goal before a couple of bookings for the visitors broke up the play.
Huddersfield then doubled their lead on 62 minutes. A good burst forward from Senior and a one-two with Flo Bojaj, saw the full-back cross invitingly for defender Danny Kane to head home from close range.
Saints responded with a shot from Seager which went into side-netting before Reed whipped in a free-kick on goal which was held by Allinson.
Mugabi had another effort from a corner flash wide before Gazzaniga was forced into a smart save at the other end to keep out Hanson’s rising shot from inside the area.
Pockets of space began to open up in the closing stages as Hesketh worked Allinson with a low shot, while Sims headed over late on. Seager was booked for simulation inside the area and then forced a good save from Allinson in added time.
Those missed chances would only add to the frustration of what was, overall, a disappointing night for the team.
Southampton team: Paulo Gazzaniga; Bevis Mugabi, Alfie Jones, Jack Stephens, Josh Debayo; Harrison Reed, Dominic Gape (c) (Armani Little 77); Jake Hesketh, Josh Sims, Sam Gallagher (Olufela Olomola 83); Ryan Seager. Unused substitutes: Harry Lewis (GK), Stuart Wilkin, Ollie Cook
Booked: Mugabi (41), Seager (90)
Huddersfield team: Lloyd Alinson; Jacob Hanson, Jack Senior, Regan Booty, Will Boyle (c), Danny Kane, Ronan Coughlan (Jamie Spencer 90), Philip Billing, Jake Charles (Jack Boyle, 90), Flo Bojaj (Rekeil Pyke 75), Duane Holmes. Unused substitutes: Tadhg Ryan (GK), Fraser Horsfall
Booked: Holmes (57), Kane (59), Pyke (90)
Goals: Senior (22), Kane (62)
Referee: Timothy Wood