Chelsea closed to within three wins of the title with an impressive victory.
Frank Lampard's deflected free-kick gave Chelsea the lead after 21 minutes, and Eidur Gudjohnsen added a second from close range before half-time.
Southampton rallied after the break, and substitute Kevin Phillips pulled a goal back after 68 minutes.
But the champions-elect responded in style and Gudjohnsen crowned a slick move by scoring the third from Didier Drogba's pass with eight minutes left.
It leaves Chelsea with a 13-point lead at the Premiership summit, and requiring only nine more points from their remaining seven games to clinch their first championship in 50 years.
Southampton were furious about the controversial free-kick that led to Chelsea's opener from Lampard after 21 minutes.
Referee Mark Halsey harshly punished Andreas Jakobsson for a foul on Mateja Kezman, and Lampard's free-kick took a wicked deflection off Rory Delap, leaving Antti Niemi totally wrong-footed.
It was a cruel blow to Saints, who had started well, and it needed a spectacular bicycle-kick from Niemi to stop Claus Lundekvam's wayward back-pass flying into his own net.
Niemi then saved well from Robert Huth as Chelsea pressed for a second - but it was to be only a brief reprieve as Jose Mourinho's side doubled their advantage six minutes before the interval.
Southampton's defending was wretched as Johnson evaded a series of half-hearted challenges before setting up Gudjohnsen to score from close in.
Chelsea made a change at half-time, replacing Joe Cole with Tiago.
Southampton's best option was Delap's long throw, and the ploy forced a rare save from Petr Cech when Peter Crouch rose above the Chelsea defence.
Saints made a double change after 62 minutes, sending on Phillips and Anders Svensson for Graeme Le Saux and Henri Camara.
Chelsea made a change of their own, sending on Drogba for the disappointing Kezman.
Phillips almost pulled a goal back instantly, forcing Cech to arch backwards to turn over his header from Crouch's flick.
But the former England striker made no mistake from the resulting corner, reacting quicker than Chelsea's defenders to turn home Paul Telfer's cross.
Chelsea faced an anxious finale, but Gudjohnsen eased any nerves by beating Niemi from 10 yards after a brilliant passing move that also involved Lampard and Drogba, finishing with a flourish.
Southampton boss Harry Redknapp:
"I felt the referee, who is usually good, got a few key decision wrong today.
"I don't think our keeper had to make too many saves - we weren't under intense pressure at any stage.
"There was nothing in it after 20 minutes of the game until the referee made a bad decision and Chelsea scored a fluke goal."
Chelsea striker Eidur Gudjohnsen:
"My goal was important as it killed the game for us, giving us an important three points again.
"When they got the goal back we were under a little bit of pressure.
"We had some tired legs after international week. It probably wasn't our best game but all we need to do at this stage is to keep winning."
Southampton: Niemi, Delap, Lundekvam, Jakobsson, Bernard, Telfer, Redknapp, Quashie, Le Saux (Anders Svensson 63), Camara (Phillips 63), Crouch.
Subs Not Used: Smith, Higginbotham, Davenport.
Goals: Phillips 69.
Chelsea: Cech, Johnson, Huth, Terry, Gallas, Lampard, Makelele, Gudjohnsen, Duff (Jarosik 80), Kezman (Drogba 65), Cole (Tiago 45).
Subs Not Used: Cudicini, Ricardo Carvalho.
Booked: Kezman, Tiago.
Goals: Lampard 22, Gudjohnsen 39, 83.
Ref: M Halsey (Lancashire).