Guardiola's team have been focused on rewriting the record books since clinching the English title almost a month ago and they added one last landmark achievement on the final day of the season.
Gabriel Jesus struck with virtually the last kick at St Mary's to take City to the century mark in suitably dramatic fashion.
Guardiola's wild celebration with his backroom staff showed what it meant to the Spaniard for City to achieve yet another astonishing feat.
"It's incredible, I don't have words, 100 points!" Guardiola said.
"When you win for 100 points it's something special for the club. I think it's a record that will stay for a long time.
"All season we didn't surrender, we never gave up and tried until the end. It was an amazing finish from Gabriel." City's 100-point haul comes after they set a new Premier League points record by beating Brighton in midweek, taking them past the total set by Chelsea in 2004-05.
They have also scored the most goals in a single Premier League campaign (106), won the most games (32) and amassed the most consecutive victories (18) in a season that has seen them ranked along with the best teams in the history of English football.
City finished 19 points clear of second placed Manchester United -- the biggest title-winning margin in the Premier League era -- to emphasis the gap between the runaway champions and the chasing pack.
"Numbers are numbers, they are the consequence of the way we played. We didn't play perfect for 38 games but most of the time we were so good," Guardiola added. "We were better than our opponents and the records we broke came from the way we played." - City slickers -
Fortunately for fourth bottom Southampton, the defeat didn't matter in their battle to avoid relegation as third bottom Swansea lost against Stoke, ensuring Mark Hughes' side avoided the drop by three points.
City are due to celebrate their title success with an open-top bus parade through the streets of Manchester on Monday.
But they had no intention of letting the impending party distract them on the south-coast.
City controlled first-half possession before Saints defender Wesley Hoedt headed against Claudio Bravo's crossbar from a Dusan Tadic corner.
Guardiola's men pushed hard in the second half and Raheem Sterling struck the righthand post with a deflected effort before John Stones' header from the resultant corner was tipped over by Alex McCarthy.
Guardiola introduced youngsters Brahim Diaz and Phil Foden late on, ensuring both players have registered five appearances to earn a Premier League medal -- with Foden becoming the youngest ever winner at 17 years and 350 days old.
The game appeared to heading for a draw but, six years to the day since Sergio Aguero's last-second title-winning goal for City against QPR, Jesus found space in the final moments to lift the ball over McCarthy and spark mayhem among the travelling fans.
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