The Red Devils win, backing up a 4-0 demolition at Old Trafford in August and a Carabao Cup win at the Bridge, pushes them to within three points of Frank Lampard's Blues in fourth spot as the race for Champions League qualification hots up.
The home side twice had the ball in the United net during the second half, goals from Kurt Zouma and Olivier Giroud chalked off by VAR.
It was just a second Premier League victory at Stamford Bridge in 18 years for Manchester United.
Chelsea were rocked early on when N'Golo Kante was forced off injured, with Mason Mount introduced, but Lampard will have felt Maguire should also have been going off midway through the first half.
The defender clashed with Michy Batshuayi as he attempted to shield the ball out of play for a United goal kick.
Maguire appeared to catch the forward, but VAR did not see fit to hand out any punishment.
Four minutes later and Batshuayi missed a great chance to break the deadlock, side-footing wide from 12 yards after good play from Mount and Pedro.
On the stroke of half-time Ole Gunnar Solskjaer saw his side go ahead.
Aaron Wan-Bissaka's teasing cross was glanced home by Martial at the near post, the French ace beating Andreas Christensen to the ball.
Christensen was replaced by Zouma at the interval and he soon thought he'd levelled matters.
From a Chelsea corner, Wan-Bissaka cleared a shot from Pedro off the line only for Zouma to smash it home.
Replays showed that Cesar Azpilicueta appeared to collide with Ben Williams in the run-up, though United midfielder Fred might have played a role in that movement.
At the other end, Fred seized on a mistake from Pedro and was hauled down just outside the box as the visitors screamed for a penalty.
From the resulting free-kick, Bruno Fernandes clattered the woodwork with a superb strike.
To add insult to injury for Chelsea, Maguire was then on hand to head home Fernandes' corner on 66 minutes, doubling the advantage for the visiting side and leaving Chelsea even more irate that the defender was still on the field.
The evening was summed up when sub Giroud converted from Reece James' delivery on 77 minutes, only for a VAR review to show he was marginally offside as Chelsea's hopes of a comeback were extinguished.