The Shrimpers took the lead in the third minute when skipper Kevin Maher's cross from the right blazed across the box and was stroked home at the far post by an unmarked Leon Clarke for his eighth goal in 12 games.
Huddersfield immediately pressed for an equaliser and came close when Malvin Kamara's centre from the right found Danny Cadamarteri on the far side of the box and his 16-yard shot was blocked by Steve Collis' feet.
But the hosts came closest to extending their advantage when Dean Morgan's cross from the right byline was headed by Leon Clarke and superbly palmed over from point blank range by Matt Glennon.
Southend continued to create the better chances as Huddersfield's 4-5-1 formation meant Andy Booth cut a lonely figure up front.
Cadamarteri moved up as they reverted to 4-4-2 line-up, but the Terriers found the Southend defence hard to break down.
Kamara spurned a great chance to put the Terriers level when he blazed over following some good pressure from Town.
That miss was punished 60 seconds later when Blues doubled their advantage on 58 minutes.
Morgan burst into the box and, with Glennon advancing, squared to Alan McCormack who beat Joe Skarz to the ball and tapped home.
Huddersfield pulled a goal back when Skarz's free-kick from the right was nodded on by Booth for Danny Schofield to head home his first goal of the season on 67 minutes.
Town were reduced to ten men on 75 minutes when Glennon was sent off for a professional foul after referee Mick Thorpe judged he brought down Leon Clarke.
That paved the way for 17-year-old keeper Alex Smithies to come off the bench for his debut.
But he had no chance when Mark Gower rifled a 20-yard rocket into the left-hand corner of the net six minutes from time.
Things got worse for Smithies a minute from time when McCormack headed home a fourth from Maher's free-kick from the right.
Town were reduced to nine men in injury time when skipper Frank Sinclair was also sent off for stamping on McCormack.