United, still six points behind fourth-placed Manchester City, led
when Mkhitaryan raced on to Ander Herrera's through ball and hammered
into the roof of the net.
Victor Wanyama should have levelled with a header from six yards out, although visitors Spurs created few chances despite plenty of possession.
Paul Pogba almost made it more comfortable for Jose Mourinho's side when he hit a free-kick against the post, but United ended a run of three games without a win in the league.
The game ended in disappointment for Mkhitaryan, who was taken off on a stretcher with an ankle injury in the final 10 minutes at Old Trafford and has been ruled out until Boxing Day.
Spurs missed the chance to replace Manchester City in fourth and remain fifth, three points above United.
Follow the latest reaction from Manchester United's win over Spurs
But this was an assured display, coupled with a positive result, and will give Mourinho hope that his side can now build on a troubling run of three wins in 12 league games.
A defeat would have proven extremely costly to United's hopes of claiming a Champions League spot and would have put them nine points behind the visitors.
United were able to name the same starting line-up that drew 1-1 at Everton a week ago and that consistency appeared to give them the confidence to allow Spurs plenty of possession, without feeling threatened.
Tottenham produced very little, despite their command of the ball, and it was United who were the more dangerous side through the counter-attacking pace of Anthony Martial, Herrera's neat passing and Mkhitaryan's link-up play.
It was Herrera who created the goal, dispossessing Harry Kane in the middle of the park and releasing Mkhitaryan, while Pogba showed occasional signs of menace, forcing a fine save from Spurs keeper Hugo Lloris after curling a free-kick against the woodwork.

Victor Wanyama should have levelled with a header from six yards out, although visitors Spurs created few chances despite plenty of possession.
Paul Pogba almost made it more comfortable for Jose Mourinho's side when he hit a free-kick against the post, but United ended a run of three games without a win in the league.
The game ended in disappointment for Mkhitaryan, who was taken off on a stretcher with an ankle injury in the final 10 minutes at Old Trafford and has been ruled out until Boxing Day.
Spurs missed the chance to replace Manchester City in fourth and remain fifth, three points above United.
Follow the latest reaction from Manchester United's win over Spurs
Are United finding their form?
There had been a sense that Manchester United's performances were improving this season without the results - particularly in the league - following suit.But this was an assured display, coupled with a positive result, and will give Mourinho hope that his side can now build on a troubling run of three wins in 12 league games.
A defeat would have proven extremely costly to United's hopes of claiming a Champions League spot and would have put them nine points behind the visitors.
United were able to name the same starting line-up that drew 1-1 at Everton a week ago and that consistency appeared to give them the confidence to allow Spurs plenty of possession, without feeling threatened.
Tottenham produced very little, despite their command of the ball, and it was United who were the more dangerous side through the counter-attacking pace of Anthony Martial, Herrera's neat passing and Mkhitaryan's link-up play.
It was Herrera who created the goal, dispossessing Harry Kane in the middle of the park and releasing Mkhitaryan, while Pogba showed occasional signs of menace, forcing a fine save from Spurs keeper Hugo Lloris after curling a free-kick against the woodwork.
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