City have set competition records for wins, goals scored and points acquired during their march to glory in 2017-18, although little of their usual panache was in evidence during a listless opening half at St Mary's.
The unlikely 10-goal swing required to put Saints in danger of relegation never looked to be on the cards and Mark Hughes' well-manned defence coped assuredly with mounting City pressure after the break.
That was until Kevin De Bruyne's exquisite lofted pass – a 16th league assist of the campaign for the Belgium playmaker - sent substitute Jesus clear to loft a cool finish over goalkeeper Alex McCarthy.
Southampton defender Wesley Hoedt came closest to opening the scoring before the break when he hit the crossbar in the eighth minute, while Dusan Tadic almost settled the match in the hosts' favour before Brazil striker Jesus signed off ahead of the World Cup with a thrilling last-gasp salvo.
Just to recap the goal - @DeBruyneKev floats one over the top into @gabrieljesus33 's path who produces the most exquisite of chips over McCarthy to snatch the win, and snatch the historic 100 points total!— Manchester City (@ManCity) May 13, 2018
Claudio Bravo was given another outing in the City goal and grasped an attempt from the marauding Jack Stephens at the second attempt.
Stephens' fellow centre-back Hoedt then headed Tadic's corner against the bar amid an ambling start from the champions.
Hoedt had another chance in the 25th minute but dragged wide at the far post following Tadic's latest set-piece delivery.
Sterling was the man who scored a dramatic winner at the death when the sides met in November and the England winger scythed over looking for the spectacular as a forgettable first half reached its conclusion.
John Stones just failed to get on the end of De Bruyne's teasing free-kick four minutes into the second period, which City began in the manner of a team stung by some sharp words from their manager.
In the 56th-minute Fernandinho should have done better than smash a volley horribly over from inside the Southampton box and Jesus was introduced in place of Fabian Delph to give them an attacking focal point.
The pressure was piling up for Southampton, with Sterling crashing a deflected shot against the post and Stones forcing McCarthy to tip over from the resulting corner before De Bruyne fizzed one wide from the edge of the box.
A twinkle-toed Tadic almost won it for Southampton in the 78th minute – dancing around Bravo but seeing Fernandinho clout his shot off the line.
City academy products Brahim Diaz and Phil Foden came off the bench to make their fifth appearances of the season, meaning they will both collect a league-winners' medal.
And the teenagers had a front-row view as Jesus capitalised on De Bruyne's expert service in ice-cool fashion, prompting a jubilant Guardiola to leap on to the field – another piece of history achieved by his superb team.
Key Opta stats:
- This is the first time in his career that Pep Guardiola has won 100 points in a single season as manager.
- Manchester City trailed for a total of just 153 minutes in Premier League matches this season – the fewest by a side in a single campaign.
- The Citizens set a new Premier League record for the biggest goal difference in a single season (+79).
- Before becoming Manchester City manager in 2008, Mark Hughes was unbeaten against them in the Premier League (W4 D4 L0). Since leaving, he’s won only two of his 14 league meetings against the Citizens (D3 L9).
- Kevin De Bruyne provided more assists than any other player in the Premier League this season (16). He also set a record for most wins by a player in a single PL season (31).