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Fulham shocked the Red Devils at Craven Cottage as Ademola Lookman fired Scott Parker's men into the lead in the fifth minute of the clash on Wednesday.
However, United managed to pull back an equaliser through Edinson Cavani to send both sides into half-time with the scores at 1-1.
Pogba, who scored in United's 1-0 win over Burnley to send them top of the table last week, came to his side's rescue in the second half.
The 27-year-old French midfielder received the ball outside of the box and managed to find space from two Fulham players before unleashing a bending strike past Alphonse Areola.
Fulham were unable to snatch back an equaliser as United took home an important three points in the nail-biting Premier League title race.
United boss Ole Gunnar Solskjaer told BT Sport after the 2-1 win: "I think we started slow, but after their goal I felt we played well. We needed to wake up and after that we played really well.
"We don't do offsides really, we should follow the run. We had not woken up but good reaction.
"Fantastic goal by Paul and we had some other chances to finish the game, but, of course, when it is just one goal and the players they put on, it is going to be like heart in your mouth.
"He [Pogba] has really come on. He is fit, he can play in midfield and he can play wide. That is key with Paul, getting him match fit and running fit and he is at the moment. He played very well."
United move two points clear at the top of the table ahead of Manchester City, though Pep Guardiola's men have a match in hand.
The Red Devils will return to action on Sunday when they welcome Liverpool to Old Trafford for their fourth-round FA Cup clash.
Solskjaer's men will resume their Premier League campaign next Wednesday as they host Sheffield United at Old Trafford.
Featured Image Credit: BT Sport
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