The Blues hit four goals without reply with a classy, dominant performance at the Etihad.
The visitors held out for 20 minutes before Joao Cancelo gave City the lead.
Phil Foden's fine form continued with a delightful chip on 32 minutes and Riyad Mahrez wrapped up three points four minutes into the second-half with a clever volley.
It was wonderful football from the champions throughout, but there was one thing missing - an Erling Haaland goal.
The Norwegian had hit the woodwork and gone close several times but it looked as though it was going to be a rare day without adding to his incredible tally - until finally clever play between Kevin De Bruyne and Cancelo saw the latter's pinpoint cross drilled home by Haaland on 65 to complete a 4-0 win.
As has been the case in recent seasons, Southampton started the game looking organised and determined, pressing high and trying to stifle City’s attacks with men behind the ball.
Yet City’s first real opportunity came when Riyad Mahrez forced a good save out of former Academy keeper Gavin Bazunu on two minutes, with the Republic of Ireland international clawing a rising shot away.
Mahrez had another chance shortly after as he arrived in the box on the end of a deep cross from Cancelo on the left but his volley went well over.
Then Phil Foden sent Erling Haaland clear and there was only one expected outcome as the prolific striker approached the box, but his low shot struck the inside of the post, rolled across the empty net and eventually out of play.
Was it set to be another afternoon of frustration against Ralph Hasenhuttl’s side?
The answer came a few minutes later as Cancelo drifted past one challenge on the edge of the box before sending a low drive across Bazunu and into the bottom right corner with 20 minutes played.
It was a typically classy finish by the Portuguese.
City had started to pick holes in the Saints formation, with the chances starting to come thick and fast and it was a matter of when, not if, that slender lead would be doubled.
The second of the afternoon came on 32 minutes and it was another goal assisted by Kevin De Bruyne who powered forward before playing a pass to Foden who drew Bazunu off his line before expertly chipping the ball over him and into the net.
What had already looked like a mountain to climb for the visitors became an insurmountable challenge within four minutes of the restart as Rodrigo picked out Mahrez's clever back post run with a lofted pass and the Algerian volleyed the ball into the turf and past Bazunu to make it 3-0.
Haaland had worked tirelessly all afternoon, but his efforts were finally rewarded on 65 minutes when he connected with the impressive Cancelo's low cross to send a low shot past Bazunu to make it 4-0.
It's his 20th of what is rapidly turning into a wonderful debut season for the Club - though he barely celebrated, perhaps feeling he should have found the net sooner, such are his lofty standards.
There were a few more half-opportunities, but no further scoring as City's superb start to the season continued.
Ake and Akanji solid again
They won’t grab the headlines for being tidy and efficient, but both Nathan Ake and Manuel Akanji gave impressive performances yet again against Saints.
Neither defender has put a foot wrong this season and Akanji filled in superbly at right-back on this occasion.
Both add a rich depth to the Blues’ defensive unit and give Guardiola a number of options to rotate and rest his defenders whenever he sees fit.
Bright, energetic and inventive from the kick-off, Foden is shifting through the gears and hitting peak form as we move into autumn.
A goal and an assist for the England winger who bagged a treble in last weekend's Manchester derby - not a bad day's work!
Foden seems to be forging an excellent understanding with Erling Haaland, too - a frightening prospect for any opposition defenders.
MAN OF THE MATCH
Joao Cancelo scored the opener and set up the last goal of the afternoon with a classy performance during his time on the pitch.
The Portuguese is evolving into one of the best and most versatile full-backs in the world and is a crucial part of Guardiola's plans.
What it means…
City return to the top of the Premier League for at least 24 hours, with Arsenal in action tomorrow.
The Blues are two points clear of the Gunners who have a game in hand, with the champions remaining unbeaten in league and cup this season.
City travel to Copenhagen looking to book a place in the Champions League Round of 16 on Tuesday evening.
Victory will ensure progression to the knockout phase and the game kicks off at 17:45 (BST).
Then it’s back to Premier League action with a trip to Anfield to face Liverpool on Sunday 16 October, with a 16:30 (BST) kick-off.
Pep Guardiola reaction
"in general we played very well against a team we have struggled against a lot.
"We changed our set-up, our build-up. We created chances and we had a feeling those upfront could have been more clinical, but it’s fine.
"After a game every three days the players react like who they are."
City: Ederson, Cancelo (Gomez 70), Ake, Akanji, Dias, Rodrigo, De Bruyne (Alvarez 70), Bernardo (Lewis 70), Foden (Grealish 58), Haaland, Mahrez (Palmer)
Subs: Ortega Moreno, Gundogan, Laporte, Gomez, Wilson-Esbrand
Southampton: Bazunu, Walker-Peters (Larios-Lopez 70), Salisu, Bella-Kotchap, Perraud, S Armstrong (Djenepo 6), Ward-Prowse, Diallo, Aribo (Mara 79), A Armstrong (Elyounoussi 66), Adams
Substitutes: McCarthy, Maitland-Niles, Lyanco, Caleta-Car, Walcott
Stats and facts
- City are the first club to score at least three goals in nine games since Wolves in 1959 (W7, D2).
- It's one defeat in 37 league matches for City, a 3-2 home loss against Spurs in February.
- Erling Haaland has scored 15 times in nine Premier League appearances, including a hat-trick in each of City's last three home games in the division.
- Kevin De Bruyne has provided nine league assists this season, equalling his tally from 2021-22.
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