It is the second consecutive campaign Saints have suffered a 9-0 thrashing after Leicester last season at St Mary's equalled the record set by United against Ipswich in 1995.
Manchester United returned to winning ways in ruthlessly emphatic fashion with a Premier League record-equalling 9-0 home win over Southampton, who finished Tuesday's game with nine men.
The victory moves Ole Gunnar Solskjaer's side level on 44 points with leaders Manchester City although United have played two more games, with City travelling to Burnley on Wednesday.
Substitute Anthony Martial scored twice for United after the break in a result that equals the club's 1995 win over Ipswich Town and Southampton's defeat by the same 9-0 scoreline at home to Leicester City in 2019.
"We've been waiting for them to show the magic and it was a night for them to go and enjoy it. We've not had many times where we could just enjoy the second half," said Solskjaer.
"You get lots of confidence from a performance like this, scoring goals is always good for a team."
Saints, already weakened by injuries, had to play with 10 men from the second minute after midfielder Alexandre Jankewitz was sent off and they went down to nine men when defender Jan Bednarek was dismissed four minutes from time.
A bad night began after 79 seconds when Swiss Jankewitz made a dangerous high challenge on Scott McTominay, which left the United midfielder with stud marks on his thigh, and referee Mike Dean had no hesitation in showing the red card.
"When the game starts like it does it's always if you can get the first goal as we have seen so many examples of 10 men closing up shop and getting a draw," added Solskjaer, who was pleased to see his side play with such freedom.
Aaron Wan-Bissaka put United ahead in the 18th minute, sliding in at the back post to turn home Luke Shaw’s curling cross.
Marcus Rashford added the second in the 25th with a confident first-time finish after good work from Shaw and Mason Greenwood down the left.
A Bednarek own goal, from a low Rashford cross, made it 3-0 before Edinson Cavani headed home the fourth in the 39th minute.
Dean then awarded United a penalty when Kayne Ramsay brought down Cavani, who suffered an ankle injury and had to be substituted at halftime, but VAR ruled the foul had taken place just outside the box.
Yet the video official worked in United's favour after the break when Che Adams looked to have pulled a goal back for the visitors but it was ruled out on review for the tightest of offside margins.
A miserable night for Saints
French forward Martial blasted in the fifth from a tight angle after 69 minutes and McTominay made it 6-0 with a sweet drive from the edge of the box in the 71st.
Polish defender Bednarek's miserable night was completed when he was harshly sent off, conceding a penalty when he clipped Martial and then being shown the red card after another VAR review.
Bruno Fernandes converted the spot kick before Martial added his second in the final minute of normal time and Dan James made it nine in stoppage time.
Saints boss Ralph Hasenhuettl endured the second 9-0 loss of his time with the club but said his team would recover as they did after the hammering from Leicester.
"What can I say? It is horrible but we stood up after the first 9-0 and we have to do that again. I said at the time we do not need it again but when we have it again you have to take it," he said.