A second-half strike from Ashley Nathaniel-George secured a valuable three points for Southend and saw Town fall to a second successive 1-0 defeat at The EnviroVent Stadium.
In a feisty encounter that saw six bookings Town were left to rue an effort from substitute Brendan Kiernan that crashed against the bar just minutes before falling behind.
Simon Weaver made just the one change from the side that was defeated at home to Morecambe a week ago, with Warren Burrell returning the starting line-up in place of Ryan Fallowfield.
The visitors, mired in relegation trouble, winless in seven and having netted just once during this spell wielded the axe with James Olayinka, Simeon Akinola, Tom Clifford and Emile Acqua all coming into the side.
This also meant that there were just two faces in today’s starting line-up that were present in the opening day line-up that Town defeated 4-0 at Roots Hall.
Despite their recent struggles the visitors started in spirited fashion with an early curling Nathaniel-George effort being tipped wide at full-strength by James Belshaw.
From the resulting corner Town mounted a quick counter with a raking George Thomson pass picking out Josh McPake, who teased his marker before unleashing a drive that Mark Oxley did well to palm clear.
The physical Emile Acquah was played in by Nathaniel-George on 20 minutes but after working himself into a dangerous position his finish lacked the power to test Belshaw.
Shortly after Town had the ball in the net when Will Smith bundled home from Thomson’s free-kick but he was adjudged to have been off-side.
With Town’s wingers switching positions throughout the half McPake had licence to roam around the attack and his mazy run saw him slalom through the Southend defence but he couldn’t find the finish that the build-up deserved.
Town hopes were dealt a blow shortly before the break when Simon Power went down with a hamstring injury and he was replaced by Kiernan.
McPake was again in the thick of things on the stroke of half-time when he was brought down in an attacking position that saw Jason Demetriou become the first name in referee Hudson’s book.
Simeon Akinola almost put the visitors ahead on 52 minutes when he profited from Warren Burrell’s mis-judged back pass with only Belshaw at his best keeping the score on level terms.
Acquah then volleyed wide as Southend sensed a real opportunity to get a valuable three points with temperatures rising on and off the pitch after a clash in front of the respective benches.
Weaver made his second change of the day when Mark Beck replaced Aaron Martin and Town were inches away from taking the lead just after when Jack Muldoon’s cross was met first time by Kiernan who saw his shot rebound off the bar to safety.
With just over twenty minutes left Southend got their goal when Alan McCormack’s shot was saved by Belshaw but Nathaniel-George was on hand to pounce on the loose ball and hit home.
Town’s third change was forced upon them when McPake’s day was curtailed through injury with the Scot replaced by Ed Francis.
With the lead behind them, the visitors left nothing to chance and threw everything at the ball in order to secure the points.
Town continued to press and got bodies forward but despite six minutes of injury time they couldn’t find a way through to create the opportunity to take something from the game.
Harrogate Town: Belshaw, Burrell, Jones, Smith, Hall, Power (Kiernan, 38), Falkingham, Thomson, McPake (Francis, 70), Martin (Beck, 62), Muldoon.
Subs not used: Minter, Fallowfield, Williams.
Booked: (Hall, 87)
Southend United: Oxley, McCormack (Taylor, 76), Hobson, Olayinka (Holmes, 70), Akinola, Clifford, Acquah, Nathaniel-George (Bwomono, 90+5), Demetriou, Ferguson, White (Cordner, 45).
Subs not used: Seaden, Goodship, Mellis.
Goals: Nathaniel-George (68)
Booked: Demetriou (38), McCormack (63), Hobson (66), Nathaniel-George (90)
Referee: Shaun Hudson.