Liverpool moved 22 points clear of second placed Manchester City - the largest ever lead in English football's top division.
Jurgen Klopp had insisted pre-match that Southampton would be a tough nut to crack and the first half was indeed a battle that he expected.
But a rejuvenated Liverpool came out with a much more positive approach in the second half. A brilliant 45 minutes which saw the reds hit four goals without reply.
Alisson, Alexander-Arnold, Gomez, Robertson, van Dijk, Wijnaldum, Henderson, Fabinho, Oxlade-Chamberlain, Salah, Firmino
The ever masterful Roberto Firmino supplied three of Liverpool's goals.
Danny Ings should be selected for England, said Jurgen Klopp in the matchday programme. And he was very busy in the first half - tormenting the Liverpool defence, but he couldn't add to his 14 league goals this season.
Firmino had a strong case for a first half penalty - but both the referee and VAR elected against it.
Both Robbo and Firmino were involved in the opening goal, with backheels in the build up before Oxlade-Chamberlain smashes the ball into the net.
Trent Alexander-Arnold's sweeping pass found Firmino on the wing - he powered forward into the area and at the last minute provided a no-look pass backwards to Jordan Henderson who drilled a second goal.
Henderson then provided a through ball for Salah to chip over McCarthy in the Saints goal.
And as 90 minutes flashed on the Anfield clock, the reds added a fourth and Salah grabbed his second. Firmino involved again, providing the assist, before Salah scrappily bundled the ball into the net.
Liverpool have equalled Man City's Premier League record of 20 consecutive home wins and the club have now won an astonishing 100 points from their last 102.
The reds have also won 108 points from their last 38 games - another record points haul over a traditional season's length of games.
Can anybody stop Liverpool this season?