Ole Gunnar Solskjaer’s side put the Saints to the sword with a 9-0 victory, while Everton also returned to winning ways by overcoming Leeds United at Elland Road.
There can be no better way to get a title charge back on track than equalling the biggest ever Premier League victory, with Man United responding to a two-game winless run in emphatic style on Tuesday night.
The Red Devils were helped by the fact that Southampton ended the game with nine men and utterly collapsed from the moment the first of those was sent off in the second minute, but Man United still had to hold up their end of the bargain and showed absolutely no mercy in doing so.
Solskjaer will also be pleased with the fact that the goals were spread around the team too; Man United became only the second team to have seven different scorers in a Premier League match, with Anthony Martial the only one to register more than once.
The victory means that United are now the leading scorers in the league this season, but more importantly it keeps them in touch with table-toppers Manchester City, who face a trip to champions Liverpool this weekend.
It was also a swift return to winning ways at Old Trafford following their shock 2-1 defeat to Sheffield United in their previous home game, meaning that the Red Devils have now won five of their last seven top-flight outings on their own turf, having gone six without victory before that.
Another triumph on Saturday would send them level on points with Man City until Sunday at least, and it was a win over Everton in the reverse fixture at Goodison Park which began the run which catapulted them into title contention.
That result in November continued United’s formidable record in this fixture, with Everton having won just one of the last 11 Premier League meetings.
The Toffees have had even less joy at Old Trafford, losing 20 and winning just one of their last 27 Premier League visits to Man United stretching back to 1992.
Manager Carlo Ancelotti has had more success than that on a personal basis with victories at Old Trafford with AC Milan and Chelsea in that time, and he could follow Jose Mourinho as the only visiting managers in the Premier League era to win away to Manchester United with three different clubs.
The veteran Italian joked that he hoped Man United had used up all of their goals in the hammering of Southampton, but he will be quietly confident of coming away from Manchester with something given Everton’s recent form.
A surprise home defeat to Newcastle United is the only blot on Everton’s copybook over the past month or so, and they quickly bounced back from that disappointment to beat Leeds on Wednesday night.
The victory at Elland Road was their fourth in a row on the road – their best run for more than 35 years – and should they continue that run on Saturday then they would make it five top-flight away wins on the bounce for the first time since April 1970.
Indeed, Man United themselves are one of only two teams to have won more away games than Everton this season, with the Toffees’ tally of seven already their most in a single campaign since 2013-14.
All of that leaves Everton sixth in the Premier League table, just four points adrift of champions Liverpool and crucially with two games in hand over their Merseyside rivals in fourth.
Champions League qualification is still effectively in their own hands, then, and victory at Old Trafford would be another firm statement of their credentials.