Midfielder Michael Tonge scored six minutes before the interval with Phil Jagielka and Jon Stead striking in a ten-minute spell to kill off the Hammers.
Neil Warnock reshuffled the side that lost 2-1 to Newcastle last week, in an effort to stop the rot after three defeats in a row.
West Ham, whose run of three successive victories had handed them a lifeline, carved out an early opening, Carlos Tevez scooping the ball over the top from 14 yards before a blunder let in the Blades.
Keith Gillespie, in space on the right flank, was given time to pump a long ball into the goalmouth, James Collins mis-kicked 12 yards out and the unmarked Colin Kazim-Richards ballooned the loose ball over the target.
The Blades, who had surrendered a ten-point cushion to drop back into the bottom three, and backed by a 30,000 plus crowd, tested West Ham on 20 minutes.
Kazim-Richards caused problems on the left before French striker Christian Nade stepped in to fire in low shot that was blocked six yards from goal.
The London side, with Tevez proving a handful, earned a corner in the 29th minute after catching Sheffield United on the break.
Matthew Etherington picked out Bobby Zamora lurking at the far post but the striker, who grabbed the winner against Arsenal last week, pulled his header wide. Minutes later Lee Bowyer saw his driving header flash inches wide as West Ham picked up the pace.
Sheffield United swept ahead in the 39th minute after Anton Ferdinand, booked two minutes earlier, bundled over Nade a yard from the edge of the area. Tonge stepped forward to score a spectacular goal, smashing his free-kick into the top right-hand corner.
Mark Noble tried his luck with a long-range strike which flashed over the bar before Paddy Kenny pulling off a stunning stop as Sheffield United clung onto the lead.
Tevez sparked the chance as he weaved towards the area before picking out full-back Lucas Neill who drove in a low strike from 15 yards as Kenny dived to his right to pull off a one-handed save.
Tevez should have scored minutes later after another darting run left two defenders flat-footed. But the Argentinian pulled his close-range shot over the bar before United added a second, centre-back Jagielka connecting with a Gillespie corner to score with a text-book header from ten yards.
Stead finished off the London side 12 minutes from time cutting inside from the right flank to drill his low shot beyond the helpless Robert Green and into the far corner.