Ole Gunnar Solskjaer’s side got off to the worst possible start when the ball deflected off Luke Shaw for an own goal in the second minute. But, United captain Harry Maguire put his side level from a corner in the 23rd minute.
The visitor should have gone ahead from the spot after Marcus Rashford was fouled, but Newcastle goalkeeper Karl Darlow was up to the task, beating the penalty from Fernandes away with his forearm. However, the shotstopper appeared to be troubled by an injury to his left groin and Fernandes made no mistake four minutes from time.
The Portuguese finished off a superb counter-attack by lashing the ball into the top right corner to give his side the lead. Newcastle crumbled in the final minutes as right-back Aaron Wan-Bissaka netted his first senior goal in stoppage time. Rashford added a fourth with a cleverly-timed run and cool finish to complete the rout.
In La Liga, Barcelona had a bad day at the office as it lost 0-1 to Getafe, hours after defending champion Real Madrid went down to Cadiz by the same margin.
PREMIER LEAGUE: Newcastle United 1 lost to Manchester United 4; Manchester City 1 beat Arsenal 0; Sheffield United 1 drew with Fulham 1.
LA LIGA: Getafe 1 beat Barcelona 0; Real Madrid 0 lost to Cadiz 1.
SERIE A: Crotone 1 drew with Juventus 1; Inter Milan 1 lost to AC Milan 2.
BUNDESLIGA: Arminia Bielefeld 1 lost to Bayern Munich 4.