After the disappointment of home losses to Brentford in the Premier League and Real Madrid in the UEFA Champions League quarter-finals in its previous two outings, Chelsea was back on song on the south coast.
Marcos Alonso, Mount, Werner and Kai Havertz all hit the back of the net as Thomas Tuchel's side blew the Saints away and surged into a four-goal lead inside just 31 minutes.
Werner and Mount were on target early in the second half to complete the rout and open up an eight-point gap to fifth-placed Arsenal, which lost at home to Brighton and Hove Albion.
The pressure from Chelsea was incessant early on and it took the lead when Alonso drilled home a cushioned pass from Mount, who rifled in a brilliant second from 20 yards.
After hitting the woodwork twice, Werner finally had a goal when he pounced on a loose header from James Ward-Prowse at the halfway line and held off Jan Bednarek before rounding Fraser Forster.
Havertz tucked home a simple finish in the 31st minute when Werner's shot came back off the upright, and only a trio of strong saves from Forster stopped the gap increasing before half-time.
The onslaught continued after the break with Werner rolling the ball into an empty net after Forster parried N'Golo Kante's dink straight to him.
Edouard Mendy kept Che Adams at bay on a rare Saints attack and Chelsea punished his miss when Mount converted on the follow-up after Forster kept Christian Pulisic and Werner out.
Alonso and Reece James went close but Southampton was able to get to the final whistle without conceding another goal, although Chelsea's confidence will have been sufficiently boosted before its second leg against Madrid on Wednesday (AEST).