Following a goalless first half, Lee Bowyer and a Luke Young own goal soon put Alan Curbishley's side on the way to victory, before fit-again Dean Ashton wrapped it all up on the hour with his first strike since the 2006 FA Cup final.
Separated by only a single goal's difference in the table, these two in-form sides had each gone into the international break with back-to-back victories in the Carling Cup and Premier League.
And while Curbishley was forced to replace Anton Ferdinand (knee) with James Collins following the runaway 3-0 win at Reading, Boro - just one place below in 12th-spot - were unchanged from the side that had beaten Birmingham City 2-0 a fortnight earlier.
West Ham certainly enjoyed the livelier start as Mark Noble had a low 25-yarder deflected just wide, before Ashton saw his 13th-minute tap-in ruled out by a raised offside flag.
Boro gradually battled their way into the contest and on 18 minutes Jeremie Aliadiere - who was previously on loan at Upton Park - had the best chance of the first half, when Mido brilliantly sent him clear, but the Frenchman curled his 12-yarder wide of the helplessly exposed Robert Green and onto the keeper's left-hand post.
The luckless Aliadiere then spooned another shot into Green's arms before retiring with a hamstring injury on the half-hour, as the lively Tuncay Sanli entered the fray.
West Ham had also been made to make an unwelcome switch when Craig Bellamy limped away to be replaced by Carlton Cole midway through the opening period.
And of the two replacements, it was the Turkish star, Tuncay, who made the first impression with a telling burst down the left flank but, fortunately, Green was at his brilliant best to divert the dangerous cross away from Stewart Downing to keep it goalless at the interval.
West Ham may have been wobbling during those latter stages of that opening period, but by the hour mark they were home and hosed after galloping into a three-goal lead.
Within 20 seconds of the restart, man-of-the-match Hayden Mullins found Cole, who picked out Bowyer with the perfect pass.
The midfielder, who had scored his first-ever Hammers goal in the previous home game against Wigan Athletic, got the better of his former Leeds United team-mate, Jonathan Woodgate, before rifling a low 18-yarder past the groping left arm of Mark Schwarzer to break the deadlock.
Cole was in creative mood five minutes later, too, when he sent an unplayable cross into the heart of the Boro defence, only for the sliding Luke Young to divert the ball beyond the helpless Schwarzer to double the deficit.
Having taken that commanding lead, the Eastenders almost paid for their complacency at the back, where Tuncay was twice foiled by Green's brilliant point-blank stops and, when Fabio Rochemback sent the Turkish star racing clear, his chip over the advancing Hammers' keeper bounced agonisingly onto the crossbar.
A Boro goal would have set up a nervous ending but, on the hour mark, the red-booted Ashton steadied the nerves when he beat Andrew Taylor at the far post and slid Matthew Etherington's telling, deep, low left-wing cross into the net, to seal what proved to be an emphatic Hammers victory.