Sheffield United's relegation from the Premier League was confirmed as Newcastle recovered from a sluggish start to thrash Chris Wilder's side at St James' Park.
Anel Ahmedhodzic gave the visitors a deserved early lead, nodding home Gustavo Hamer's inswinging cross from close range.
The Blades carved out several opportunities to double their advantage as Newcastle struggled to gain a grip on proceedings, but the home side were level when Alexander Isak drilled home from Jacob Murphy's pass in the 26th minute.
Ben Brereton Diaz had a goal-bound shot blocked by Dan Burn and Mason Holgate headed against the woodwork on the half-hour mark, but the visitors fell behind early in the second half when Bruno Guimaraes steered Anthony Gordon's delivery into the far corner.
Isak registered his 23rd goal of the season from the penalty spot after Gordon was brought down by Holgate, before the unfortunate Ben Osborn bundled into his own net for Newcastle's fourth.
Callum Wilson came off the bench for the hosts to score his first top-flight goal since October.
Sheffield United were awarded a late penalty, but the decision was overturned by the video assistant referee who ruled Magpies substitute Alex Murphy had won the ball in a challenge with Jayden Bogle.
The defeat leaves the Blades 10 points adrift of safety with only three games remaining, while Newcastle stay seventh and are well placed to secure a spot in Europe next season.
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