However, Jose Mourinho's men could only manage a 0-0 draw at Old Trafford, meaning they drop down to third in the Premier League table.
The clash saw the return of Henrikh Mkhitaryan to Man Utd's starting XI, having been somewhat exiled by Mourinho in recent months.
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After a great start to the campaign, Mkhitaryan has found himself well and truly out of the picture at United of late, but he lined up on the left-wing, with in-form Jesse Lingard given the free role.
Juan Mata and Marcus Rashford, who replaced the injured Romelu Lukaku, showed some moments of quality in the first-half, but the same couldn't be said for Mkhitaryan.
Mkhitaryan's performance v Southampton
The 28-year-old produced a number of over-hit crosses when United had worked the ball into fairly decent areas, while his corners failed to beat the first man on more than one occasion.
For someone so technically gifted, Mkhitaryan was misplacing an astonishing amount of passes, and United fans took to Twitter to share their opinion on his disappointing display.
Man Utd fans react to Mkhitaryan's display
It's safe to say that the Armenian Player of the Year felt the full wrath of Man Utd supporters during the match, who were destroying his lack of end product - among many things.
Whether it's a lack of form, confidence, or both, Mkhitaryan didn't grasp the opportunity Mourinho gave him against the Saints and many fans believe his time at the club may be up.
Check out the best of the reaction below:
Mkhitaryan looked slightly better in the second half, but as the Red Devils pushed for the all-important opener, he was hooked by Mourinho in favour of Anthony Martial.
In fact, as the Frenchman replaced Mkhitaryan in the 65th-minute, the Old Trafford crowd appeared to sarcastically cheer the latter's departure.
With the January transfer window on the horizon, it would come as little surprise to Man United fans were Mkhitaryan to leave the club in search of form and regular first-team action.
Do YOU think Mkhitaryan is good enough for Man Utd? Do YOU think he will leave the club in January? Have YOUR say in the comments box below!