The win with first-half goals from Jonas Gutierrez and Andy Carroll were added to by Kevin Nolan and Wayne Routledge, before Brett Ormerod managed a late consolation.
The victory means United remain six points clear of West Brom with four matches to play, while the Baggies are left with just three fixtures
Chris Hughton was forced into one change from the side which beat Sheffield United on Monday, with bug victim Jose Enrique replaced by Tamas Kadar, making his ninth start of the season.
Blackpool went into the match searching for a double over United and sitting one point outside of a play-off position.
Newcastle stormed ahead after just 12 minutes through Gutierrez. Kadar played in the Argentinian down the left, who slipped two defenders to see his shot deflect beyond Matt Gilks to start the Spiderman celebrations.
It then got better before the break when Carroll netted a second for United to erase memories of that rare early-season defeat at Bloomfield Road.
Throughout the season the telling accuracy of Danny Guthrie from set-pieces has been paramount in the United success story and the midfielder was as accurate as ever when he planted the ball at pace on the forehead of Carroll, who gave Gilks no chance.
Carroll then returned the favour with a penetrating pass of his own only for Guthrie to squander the opportunity in front of goal.
Early into the second half and Carroll once again supplied the ammunition for strike partner Peter Lovenkrands, only for the Dane to head beyond Gilks and against the woodwork.
More United goals looked as if they would follow and it was no surprise when red-hot Nolan made it 3-0 on 62 minutes.
Shell-shocked Blackpool were hit again after 77 minutes when Routledge grabbed his second goal for the club, before Ormerod pulled back a consolation for the Tangerines five minutes from time.