Goals from Naby Keita, Mohamed Salah and Jordan Henderson saw the Reds overcome Shane Long's ninth-minute opener at St Mary's on Friday.
Here are five talking points from the south coast...
Defiant Liverpool turn it around again
The character and resilience of this Liverpool team is clear to see. They have now won seven of their last eight Premier League games when conceding first.
Jürgen Klopp's side recovered from an early setback to secure a vital three points in the title race.
"It’s brilliant," the boss said of his players' mentality afterwards.
Henderson and James Milner came off the substitutes' bench after 59 minutes and inspired the comeback as Liverpool left it late once again.
Salah's counter-attacking goal to put the visitors 2-1 up arrived in the 80th minute, while Henderson's impressive cameo was rewarded with a close-range finish four minutes from time.
Salah breaks another record with crucial goal
No player has scored 50 Premier League goals for Liverpool quicker than the Egyptian. Bringing up that figure after 69 appearances sees him take the record off Fernando Torres (72).
And what a way to do so.
After Liverpool successfully cleared a Southampton corner, Salah picked up possession deep in his own half before driving towards the hosts' penalty area.
Approaching Angus Gunn's goal, he could have played in Roberto Firmino to his left. Instead, the reigning Golden Boot holder had the confidence and ability to fire home and put Liverpool ahead.
"I think that's goal No.50 for Liverpool in the Premier League, that's special," he said post-match.
Reds back on top
The nip-and-tuck nature of this title race continues. Liverpool are now at the summit once again, having been leapfrogged by Manchester City in midweek.
"Liverpool, top of the league," chanted the joyous travelling Kop.
The Reds are back in league action next Sunday when Chelsea visit Anfield. City, meanwhile, visit Crystal Palace a couple of hours earlier.
Keita nets timely first goal for Reds
The midfielder certainly picked a good moment to open his account for the club.
A resurgent Southampton threatened plenty throughout the first half, but Keita was on hand to round off a good spell of Liverpool pressure in the 36th minute.
In the second phase of an attack, the No.8 produced a giant leap at the back post to nod in and put the visitors level. He became the third Guinean to score in the Premier League after former Red Titi Camara and Kamil Zayatte.
It was a welcome impact in what was his first Premier League start since February 9.
Trent's landmark night
On a night of significant half-centuries, Trent Alexander-Arnold got in on the act, too.
The right-back racked up his 50th Premier League appearance for Liverpool with a start at St Mary's - becoming the fifth-youngest player in the club's history to achieve the feat after Michael Owen, Raheem Sterling, Robbie Fowler and Steven Gerrard.
As we saw frequently in his previous 49 outings, Alexander-Arnold's threatening delivery was on display against Ralph Hasenhuttl's side.
It was his cross from the Southampton byline that was met by the leaping Keita for his seventh assist of the season.
It's safe to assume similar service will be present in his next 50.