John Carew set the Hammers on their way with a 12th-minute header and Blackpool collapsed after the break as a Sam Baldock double and Jack Collison's strike completed the rout.
West Ham boss Sam Allardyce had spoken during the week of his bitterness at being dismissed by Blackpool after leading them to the brink of promotion in 1996 and he gained some revenge with a dominant display at Upton Park.
Blackpool had gone into the game high on confidence after winning 5-0 last time out and they actually looked the better team until West Ham opened the scoring.
Julien Faubert crossed from the right and Carew showed good strength to hold off Matt Hill and find the bottom corner with his header.
That gave the Hammers a huge boost and they could have added a second almost immediately but Baldock was denied by Matt Gilks.
West Ham were angered when Collison split the Blackpool defence and was put through on goal but referee Andy D'Urso failed to play advantage and instead blew for a free-kick in the centre circle.
Gilks was called into action again just before the half-hour mark when his smart save spared the blushes of Hill , whose poor touch allowed Carew a clear run at goal.
West Ham continued to look threatening and Gilks again denied them a second when he saved with his right leg from Carew, before Baldock fired over.
West Ham goalkeeper Manuel Almunia was finally called into action just before the interval but had no trouble holding a low drive by Jonjo Shelvey.
A second goal looked like it would be enough to kill off the visitors and West Ham needed just two minutes of the second half to double their lead.
Blackpool tried to play a high offside trap but were left waiting for a flag that never came as Matthew Taylor's header put Baldock clean through, and the striker held his nerve to slot coolly past Gilks.
It was certainly all over four minutes later and Hill was again at fault as the ball was allowed to bounce in the area before Carew flicked the ball over Gilks and Baldock tapped in on the line.
The Seasiders conceded a fourth in the 55th minute when the ball fell to Collison on the edge of the area and his deflected volley again left Gilks with no chance.
It was a case of damage limitation for Blackpool from then on and Gilks again came to the rescue with a superb save to prevent Baldock completing his hat-trick.