Beating the Saints restored the eight point cushion after a win for Manchester United against Watford 24 hours earlier had reduced it to five.
The likes of Sergio Aguero, Gabriel Jesus, Kevin de Bruyne, Leroy Sane, Fernandinho, John Stones and others have all played huge roles in putting City where they are. But the contributions of Raheem Sterling might just be the biggest and most important of the lot.
It was Sterling's 96th minute strike that sealed the win on Wednesday, turning what looked like one point into three, and not for the first time this season.
The 22-year-old has scored as many as four absolutely crucial late goals so far in 2017/18 that have been directly responsible for giving City extra points and sending them so far clear.
Raheem Sterling has scored 3 late #PL winners and 1 late #PL equaliser this season. Hypothetically, without just those 4 goals, Man City would be 7 points worse off and the gap at the top would just be a single point. That is some going from 'Raz'.— Jamie Spencer (@jamiespencer155) November 30, 2017
Just a few days before facing Southampton, Sterling had done similar, albeit not quite as dramatically late, against Huddersfield at the John Smith's Stadium, with his 84th minute strike winning the game for City in a 2-1 scoreline.
Go back to August and only the third Premier League game of the season when Sterling scored in the 97th minute at Bournemouth in another narrow 2-1 City victory.
That vital moment had come only five days after Sterling scored an 82nd minute equaliser to spare blushes against Everton in the opening home game of the new Premier League season.
Between those four goals in the last 10 minutes against Southampton, Huddersfield, Bournemouth and Everton, Sterling has given City 10 points (three wins, one draw). Without those late and decisive interventions,City could be as many as seven points worse off right now.
Hypothetically, without Sterling popping up at the vital moments as he has done, the club's lead in the title race would be just a single point ahead of fierce rivals United. It highlights just how much of an impact the 22-year-old and his goals have had on this season.
Sterling famously arrived at City in a high profile £49m move from Liverpool in the summer of 2015 and initially struggled to translate his vast potential into consistent performances to live up to his record transfer fee.
Now, the young star appears to have turned a corner. No longer is he shirking responsibility and providing only sporadic moments of magic, he is making real tangible contributions and giving his teams goals and results that they might not otherwise have had.
"As I have said many times, he is making steps. Before he was a little bit more shy and he did not believe, but now he can do that," Guardiola said of Sterling after the Southampton game.
"I think his team-mates give him the confidence and say 'we trust in you' but then you have to have the personality to do what he did in the last minute."
His impact is absolutely clear to see.