Many home fans had already started to celebrate the goal when Erling Haaland was sent off barely a quarter of an hour into the match.
The Norwegian met the ball with a right wide side but dotted the inside of the post.
Instead, it was Haaland's teammates who got City's goalscoring going.
Left-back Joao Cancelo produced a fine solo effort to make it 1-0 in the 20th minute before Phil Foden made it 2-0 in the 32nd.
Riyad Mahrez scored 3-0 shortly after the half-time break and the victory was thus more or less secured.
The only thing missing for City was the near-obligatory goal from Erling Haaland.
The Norwegian would also deliver - eventually.
In the 65th minute, he found the gap between the Southampton goalkeeper's legs after a low pass from Joao Cancelo.
Thus, Haaland has scored in ten consecutive competitive matches for Manchester City, and 18 goals in the ten matches.
20 goals in total for Manchester City.