After a tense first half, the Hammers came to life in the second period with early goals from Mark Noble and Kevin Nolan, going on to secure a crushing win over Nigel Adkins' side
After a tense and goalless first half, Mark Noble's free-kick drifted all the way in to give the Hammers the lead just a minute after the break, with Kevin Nolan tapping on Yossi Benayoun's cross two minutes later.
Adam Lallana gave the Saints a glimmer of hope after the hour but Noble's penalty and Modibo Maiga's first Premier League goal sealed a fine win for Sam Allardyce's men.
Sam Allardyce made just two changes from the side that lost 3-1 to Arsenal last time out, James Tomkins and Yossi Benayoun coming in for Guy Demel and Ricardo Vaz Te. Andy Carroll, Nolan and Matthew Jarvis all started.
Saints' top scorer Rickie Lambert was left on the bench by Nigel Adkins, with Jay Rodriquez leading the line. Elsewhere Nathaniel Clyne returned at the back and Arthur Boruc made his debut in goal, while Gaston Ramirez was sidelined with injury.
It took 20 minutes for the hosts to finally create the first real chance of the game. Jarvis beat Clyne on the left-hand-side before swinging in a cross, Boruc could only flap the ball as far as Tomkins who headed it back at goal, only for Jos Hooiveld to nod it off the line.
Apart from one curling effort from Rodriguez that flashed past the post, the rest of the period saw very little action indeed with both sides lacking any cutting edge in the final third, the half-time whistle being met with a chorus of boos from around the ground.
Southampton had shipped 20 goals in seven games before this game and their defences were breached less than a minute into the second half as Noble drifted a free-kick into the area that snuck past everyone and went in at the far post.
Whatever Allardyce said at half-time must have been special because Nolan doubled their lead with virtually the next play of the game. Benayoun will take the credit, after his determination saw him get the better of two Saints' players before he squared for the former Newcastle man to finish with ease at the back post.
The away side rallied and created good opportunities before Rodriguez got away from Collins as the ball was played over the top, the forward then picked out Lallana who swivelled neatly before smashing the ball past Jaaskelainen.
Lambert was then introduced to the fray, and nearly made an instant impact hitting a free kick just over and heading narrowly wide. But despite the introduction of their leading scorer Saints' revival was short-lived.
Just before the half-hour mark Jose Fonte was penalised for handball inside his own area, under pressure from Carroll, and a penalty was awarded - Noble confidently firing home for his second.
Maiga then put the icing on the cake in the closing stages, netting his first Premier League goal since moving to the Hammers in the summer with a fine curling left-footed effort after he had stepped past Yoshida.