Anthony Martial stepped off the bench to fire in a priceless late winner as United deservedly earned a hard-fought win against high-flying Spurs.
United had dominated the second half without any joy but the Frenchman - who had come on for Marcus Rashford - rifled in from Romelu Lukaku's knock down in the 81st minute. Eric Bailly returned to the team as Jose lined up with a back three - Spurs, meanwhile, were without talismanic striker Harry Kane.
The Reds, seeking to respond after last week's shock defeat to Huddersfield, started brightly and went close twice early on.
Ashley Young picked out Lukaku and his cross was dealt with by Hugo Lloris, before the Spurs keeper was tested again when he pushed Marcus Rashford's free-kick from a distance around the post.
Mauricio Pochettino's side, who came into the game level on points with United, were neat and tidy in possession but largely restricted to efforts from range.
Young squared up to Dele Alli with Lukaku also involved in the melee as tensions ran high in front of an Old Trafford crowd who were baying for blood.
Half chances fell the way of Alli and Son Heung-min, but David de Gea easily dealt with both in the closing moments of the first half. United upped the ante after the interval and soon began to dominate the visitors.
Lloris saved well from Henrikh Mkhitaryan, and Ben Davies cleared the danger under pressure from the stretching Rashford. Lloris continued to earn his corn and came to his side's rescue again as he saved superbly with his foot to deny Lukaku from close range on the hour mark.
Antonio Valencia skimmed the bar with a drive, and another opportunity went the way of the Reds shortly after Martial's introduction.
The French winger linked up with Nemanja Matic and sent Lukaku away, but Lloris again snuffed out the Belgian with a smothering block.
At the other end, Alli had the game's best opening when he latched on to Christian Eriksen's excellent clipped ball, but he could only poke the ball wide when well placed.
United continued to press and came within inches of the elusive breakthrough when the lively Lukaku headed against the post after substitute Jesse Lingard had picked him out.
But the Reds were not to be denied and our persistence paid off with nine minutes to play.
Lukaku flicked the ball into the path of Martial, who raced through and fired in beyond the advancing Lloris as Old Trafford erupted.
Lingard had a late chance to seal the deal, but it did not matter as United held out for a valuable and much needed three points.
Overall team performance: 7.5/10
United Faithful Man of the Match: Ashley Young. A much-maligned player who's reborn now under Mourinho. Received a standing ovation when subbed off in stoppage time.