Frank Lampard's Blues opened the scoring at Stamford Bridge through a fine individual effort for Timo Werner. Werner doubled his tally just before the half-hour, again stealing a march on the hapless Jan Bednarek.
But Chelsea were forced out of cruise control just before the break, with Danny Ings rounding Kepa and slotting home to halve the deficit heading into the interval.
Che Adams then levelled things up after the restart, but Kai Havertz put Chelsea 3-2 in front soon after - but the Saints were level at 3-3 in injury time to deny Lampard a win as questions about his defence and goalkeeper were once again raised.
Follow all the latest match reaction with Malik Ouzia!
Chelsea XI: Arrizabalaga, Azpilicueta, Christensen, Zouma, Chilwell, Kante, Jorginho, Pulisic, Havertz, Mount, Werner.
Subs: Abraham, Caballero, Tomori, Giroud, Hudson-Odoi, Ziyech, James.
Southampton XI: McCarthy, Walker-Peters, Bednarek, Vestergaard, Bertrand, Walcott, Ward-Prowse, Romeu, Redmond, Adams, Ings
Subs: Stephens, Long, Obafemi, Valery, Tella, Diallo, Forster
Referee: Robert Jones
Ralph Hasenhuttl could opt to hand a Southampton debut to Mohammad Salisu following his summer move from Real Valladolid.
Head to head (h2h) history and results
Of the 43 Premier League meetings between the teams, Chelsea have won 24 and Southampton nine, with 10 draws.
Chelsea eased to a 4-1 win at St Mary's in October 2019, only to lose the return fixture 2-0 on Boxing Day courtesy of goals from Michael Obafemi and Nathan Redmond.