City have now won 12 of their last 13 games with the only dropped points coming in a creditable 0-0 draw at Liverpool last month.
Pep Guardiola’s men had scored 13 goals in their three previous visits to the London Stadium and had another three before half-time in another dominant display.
David Silva scored for the fourth straight game when he flicked home Raheem Sterling’s cross on 11 minutes.
Sterling’s own stunning form in front of goal continued when he tapped home Leroy Sane’s cross for his eighth goal of the season.
The roles were reversed from City’s flying wingers 11 minutes before half-time when this time Sane showed great composure to turn home the England international’s pass and Sane completed the rout in stoppage time.
In keeping with recent weeks, Liverpool were far less impressive but remain on City’s coat-tails as Mohamed Salah, Trent Alexander-Arnold and Roberto Firmino all struck in the final quarter at Vicarage Road.
Jurgen Klopp’s men rode their luck as Watford had an early goal disallowed and saw strong claims for a penalty just after the break waived away.
However, the visitors front three finally clicked 23 minutes from time when Firmino fed Sadio Mane and his cut-back was prodded home by Salah for his ninth goal of the season.
Alexander-Arnold then bagged his first for the campaign at club level with a sumptuous free-kick after opening his account for England in the international break.
And despite having captain Jordan Henderson sent-off, Liverpool added a third through Firmino a minute from time.
How United wish they had the same firepower as after a bright start they again faded and Palace held out for just a second point in seven Premier League games.
Pogba and Romelu Lukaku were fit enough to start after missing international duty for France and Belgium through injury, but failed to spark the hosts and Pogba was even withdrawn for Alexis Sanchez in the search for a winner that never came.
Mourinho’s men were even fortunate that Marouane Fellaini wasn’t shown a red card for a horrendous challenge on Palace captain Luka Milivojevic that went unpunished.
Ranieri couldn’t stop Fulham leaking goals in his first match in charge at Craven Cottage, but did secure a first win in 10 league games as Aleksandar Mitrovic scored twice to edge a five-goal thriller.
Stuart Armstrong also scored a double for Saints and opened the scoring before Mitrovic and Andre Schurrle turned the game around before half-time.
Another great strike from Armstrong levelled before Mitrovic volleyed home to spark wild scenes of celebration from Ranieri.
Leicester showed great resilience after a difficult few weeks off the field to fight back from a goal and a man down for a 1-1 draw at Brighton.
Glenn Murray opened the scoring and the visitors had James Maddison sent-off for two yellow cards in the opening 28 minutes, but Jamie Vardy’s penalty eight minutes from time secured a point.
Gylfi Sigurdsson’s solitary goal at Goodison Park was enough to see off Cardiff and continue Everton’s progress under Marco Silva.
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