Jadon Sancho scored his first goal for Chelsea as they ruthlessly capitalised on a series of Southampton errors to run out comfortable winners.
Sancho wrapped up the scoring for the Blues after goals from Axel Disasi, Christopher Nkunku, Noni Madueke and Cole Palmer had put them in control.
Saints briefly levelled at 1-1 through Joe Aribo but their capacity to self-destruct was underlined when, after falling 3-1 down, captain Jack Stephens was sent off by referee Tony Harrington for pulling Marc Cucurella's hair.
With Chelsea flying high - victory took them second above Arsenal - and their hosts bottom of the table, there was no doubting who the favourites were going into the match.
And when goalkeeper Joe Lumley failed to clear Enzo Fernandez's near-post corner, Disasi headed home from two yards out to put the visitors in front.
The lead lasted just four minutes, though, as Aribo made up for squandering an earlier chance by turning home an excellent cross from full-back Kyle Walker-Peters for a deserved equaliser.
But another Lumley mistake - this time while playing out from the back - allowed Nkunku to score in an empty net and restore Chelsea's lead.
They doubled that advantage just after the half-hour as Madueke's tricky dribbling took him past Ryan Manning before stroking the ball into the far corner.
And what already looked an uphill battle became even harder for Saints when Stephens was dismissed for pulling Cucurella's hair as the hosts prepared to take a corner.
Palmer and Tosin Adarabioyo hit the woodwork as Chelsea continued to dominate - and the second half brought further trouble for Russell Martin's struggling side.
Joao Felix headed a simple chance wide immediately after the break, Tosin again hit the woodwork in the 53rd minute and Palmer, Madueke and Nkunku all had chances to extend the lead.
It was Palmer who finally did so, scoring his ninth of the season after Nkunku's initial effort had been blocked.
Substitute Sancho then opened his Chelsea account by finishing in a one-on-one situation from Malo Gusto's through ball.
'We've got our Chelsea back'
Chelsea boss Enzo Maresca opted to make seven changes to his side - only one of which was enforced as Wesley Fofana recovers from a hamstring injury.
And the manner of the victory meant he was able to take off both Palmer and Moises Caicedo as he looks ahead to Sunday's London derby against Tottenham.
What is clear is that Maresca has flipped the mood among the Blues faithful, with chants of "we've got our Chelsea back" ringing out of a raucous away end.
At half-time, there were more cheers as it was announced Newcastle were leading table-topping Liverpool 1-0.
And while the Reds recovered to draw 3-3 at St James' Park, it is clear Chelsea fans now believe they can compete with Arne Slot's side.
Maresca's name was also bellowed out, and there were chants supporting players including Cucurella and Fernandez, who have previously been derided.
Owner Todd Boehly, too has been criticised but perhaps the plan he and the Clearlake group have insisted they have had all along is coming to fruition.
Errors, injuries and bans mount for Saints
Southampton came into the game with three players suspended, one - Lesley Ugochukwu - ineligible against his parent club and more than six injured.
At least four of those should return for the trip to Aston Villa on Saturday, but Stephens is now suspended after his inexplicable decision to pull Cucurella's hair with the video assistant referee (VAR) there to spot those types of infractions.
Lumley, too, had a night to forget, but the same could also be said for many of the club's second-string outfield players.
Saints had 70% of possession in the first 15 minutes and were competitive for the first 25, but their third big error was one too many and there was no way back.
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