Southampton's want-away midfielder Morgan Schneiderlin scored twice as Ronald Koeman's men earn their first Premier League victory during his tenure.
West Ham started well and took the lead when Mark Noble's deflected long-range effort beat a despairing Fraser Forster, who did brilliantly to prevent Ricardo Vaz Te scoring a few minutes earlier.
However, Southampton soon took control of the game as they looked to equalise. Graziano Pellè went close with a header which was cleared off the line, before they got their reward on the stroke of half-time as Morgan Schneiderlin scored a neat left-footed finish after having his initial shot saved by West Ham's Adrian.
Saints then turned it up a gear after the break, dominating every aspect of the game. West Ham couldn't string a pass together and they soon succumbed to some superior Southampton pressure. The Hammers' defence was caught napping before James Ward-Prowse delivered a near-perfect ball for Schneiderlin to tuck in at the near post.
Under previous managers, Southampton would have sat on that 2-1 lead and would've tried to see out the win on that slender lead - often a heart attack-inducing experience for Saints fans. But, Koeman's men continued to play with purpose and soon extended their lead further.
Nathaniel Clyne, who was lively as ever on the right side of defence, went on one of his marauding runs and sent in a cross which West Ham keeper Adrian couldn't deal with. Adrian palmed the cross out to new Saints striker Pellè, who smashed the ball home to secure victory for the southerners.
The result and performance must be encouraging for Saints fans, who have endured a summer of misery seeing the likes of Adam Lallana, Rickie Lambert, Dejan Lovren, Callum Chambers and Luke Shaw all leave the club.
Southampton have been soundly beaten on their last two visits to Upton Park and thoroughly deserved the victory today. This result is also the first time in 20 years a Saints side has come from behind to win a Premier League match away from home. Not a bad day all round.