Southampton made a nightmare start at Old Trafford as 19-year-old Alexandre Jankewitz was sent off just 79 seconds into his full Premier League debut for a high challenge on Scott McTominay.
Man Utd took advantage with Aaron Wan-Bissaka tapping in Luke Shaw’s cross before Mason Greenwood teed up Marcus Rashford to double the lead 25 minutes in.
Jan Bednarek then scored an own goal and Edinson Cavani headed in from a second Shaw assist to make it 4-0 at half-time.
It got even worse for Southampton when Bednarek was sent off for a clear denial of a goalscoring opportunity and Fernandes converted the resultant penalty.
Martial then struck his second of the match before Daniel James rounded off the scoring with the last kick of the match, converting Fernandes's header across the box.
United tie their own 9-0 win over Ipswich Town in 1995 and Leicester City's victory by the same scoreline at Southampton in 2019.
It means they are behind Man City on goal difference alone but have played two matches more. Southampton drop to 12th after a fourth consecutive loss.
Wolverhampton Wanderers ended their eight-match winless run as they beat an Arsenal team who had two players sent off.
Arsenal made a strong start with Bukayo Saka hitting a post and having a goal overturned for offside before they took a 32nd-minute lead.
Nicolas Pepe nutmegged two Wolves players before curling a beauty past Rui Patricio.
But the match turned in first-half stoppage time, when David Luiz brought down Willian Jose in the penalty area and was shown a straight red card for making no attempt to play the ball.
Ruben Neves converted the spot-kick and Wolves were quick to make their man advantage count.
Just three minutes into the second half, Joao Moutinho unleashed a long-range strike into the top corner to complete the turnaround with his first goal at Molineux.
Things got worse for Arsenal on 72 minutes as their goalkeeper, Bernd Leno, made a deliberate handball outside the box and was sent off for denial of a goalscoring opportunity.
The win lifts Wolves to 13th, four points behind 10th-placed Arsenal, who were beaten for the first time in eight matches and missed the chance to go sixth.
Gary Cahill's first Premier League goal for nearly four years earned Crystal Palace a turnaround win at Newcastle United.
The centre-half headed in Eberechi Eze’s right-wing cross to become Palace’s oldest Premier League goalscorer and give Palace back-to-back victories for the first time since Matchweek 2.
Newcastle had made a fast start as Callum Wilson set up Jonjo Shelvey to volley the hosts ahead inside two minutes.
But Palace hit back with two goals in five minutes, with Jairo Riedewald's shot deflected in off Ciaran Clark before Cahill's effort.
Ryan Fraser had a shot saved by Vicente Guaita and Miguel Almiron hit the top of the bar with a free-kick, but Newcastle could not find an equaliser.
Palace move up to 13th place on 29 points, while Newcastle dropped to 16th on 22 points, eight above the relegation zone.
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