The Saints set a brand new record by becoming the first and only team to beat all seven past champions in the season after their title win.
In other words, seven different teams have won the Premier League since it began in 1992-93 (Manchester United, Blackburn Rovers, Arsenal, Chelsea, Manchester City, Leicester City and Liverpool) and the Saints have now toppled them all during their respective title defence campaigns -- the only opposition ever to have done so.
Here are the games in question, and a brief review of quite how Southampton staked their claim as unlikely giant-slayers.
Southampton 1-0 Blackburn, April 9, 1996
Finding themselves hovering perilously above the relegation zone, the Saints pulled off a string of timely upsets towards the end of the 1995-96 season that ultimately saw them stay up on goal difference.
One of those vital coups came at their old ground, The Dell, where a penalty from Matt Le Tissier was enough to garner all three points against the defending league champions.
Southampton 6-3 Man United, Oct. 26, 1996
In one of the most well-remembered games of the Premier League's early years, the Saints scored six at the Dell on their way to annihilating United.
Just six days after losing 5-0 against Newcastle, United were once again humiliated by an onslaught that began when Eyal Berkovic opened the scoring with just five minutes on the clock.
Visibly enraged, Roy Keane then got himself sent off inside the first 25 minutes as Sir Alex Ferguson's shell-shocked side capitulated before his very eyes.
Southampton 3-2 Arsenal, Nov. 23, 2002
Already on a hot streak coming into the game, striker James Beattie scored his seventh and eighth goals in seven outings as the Saints overturned defending champions Arsenal at St Mary's.
Southampton 3-1 Man City, Feb. 9, 2013
Having slipped down into League One, Southampton came roaring back into the top flight in the space of just two years after winning back-to-back promotions.
They duly marked their return to the big time by toppling the mega-rich reigning champions, thumping City 3-1 at St Mary's -- Saints' first win under Mauricio Pochettino.
After gradually moving clear of the relegation zone, Pochettino's side went on to finish the season safe and sound, tucked away in 14th place.
Chelsea 1-3 Southampton, Oct. 3, 2015
The Saints inflicted yet more misery on Chelsea, who were embarking on their worst start to a league season since 1978-79 in what would prove to be Jose Mourinho's infamous annus horribilis.
Southampton 3-0 Leicester, Jan. 22, 2017
After sacking Claudio Ranieri, the manager responsible for delivering their historic 2015-16 title, Leicester didn't fare particularly well the following season.
Bobbling around in mid-table during the opening months, the formerly flying Foxes sunk down to 17th at the turn of the year following a catastrophic run of five consecutive defeats in which they conceded 12 goals and scored none in response.
Southampton 1-0 Liverpool, Jan. 4, 2021
A quarter of a century after slaying their first title-winning giant, the Saints completed the set this week by seeing off the mighty Liverpool at St Mary's.
Ralph Hasenhuttl's resurgent side went sixth in the table thanks to Danny Ings' exquisitely executed lob scored in the second minute of the tie.
On the other side of the equation, the Reds suffered a minor setback in their quest to retain the title and currently remain locked level on points at the top of table, neck and neck with old foes Man United -- who have a game in hand.