One is entrenched within the history of Europe's elite, and the other is renowned for their incredible rise through the English leagues, yet they have created an unlikely 'rivalry' which has been established away from the heated on-field battle.
Their intertwining recent history stems solely through a handful of transfer windows, a sign of the times that the modern battle takes place in boardrooms and on blanks cheques, and the latest off-field drama will finally enter the playing field and come to a head when Liverpool host Southampton on Saturday.
For almost seven-years the only relevance that existed between the two sides was that they each played in a division of English football, as the years between 2005 and 2012 saw the Saints yo-yo from the Premier League to League One, and back again.
It ensured their paths would not cross, but fast-forward five-years and it is as though you cannot mention one without the other, and not in the way either set of fans would prefer.
Such is the state of their current relationship that their exists a shared awareness that the Saints have become a feeder club to their league rivals, a one-stop shop for all Liverpool's on-field needs - much to the regularly scheduled entertainment for Southampton legend Matt Le Tissier.
Although some transfers have proved to be more successful than others for Liverpool - you be the judge - the fact remains that they have relinquished a staggering £98m to the Saints in the Premier League era - where four of the seven players still remain at Anfield.
Goalkeeper Paul Jones and striker Peter Crouch were the first to swap St Mary's for Anfield in 2004 and 2005 respectively, however, it was the players who made the switch in 2014 which broke the dam wall and established the unorthodox association between the two clubs.
The class of 2014 included Rickie Lambert, Adam Lallana, and Dejan Lovren, who were then joined by Nathaniel Clyne the following season, and most recently by Sadio Mane in 2016.
Everyone bar Lambert still possesses a locker at Anfield and are regulars for Jurgen Klopp's side, as the four have combined for 325 appearances for the Reds, scoring 43 goals across a little over three seasons.
The deep-rooted nature of Liverpool's fondness of Southampton players was continued despite their former manager Brendan Rodgers no longer at the club, as Klopp took up the mantle to first poach Mane and then return for defender Virgil van Dijk - it was as though he was contractually required to follow tradition.
The up-keeping of that tradition took Klopp to Van Dijk, a central defender who Liverpool were, and are, in desperate need of as Lovren and Ragnar Klavan continued to pose more questions than they answered.
However, their attempt to lure the Dutch centre-back was foiled after an illegal approach which led to Southampton taking the issue to the Premier League, resulting in Liverpool's embarrassing public withdrawal of their interest in the player.
This is the point in which the rivalry threatened to spill over, the Saints were understandably sick of being at Liverpool's beck and call and shut the door on any possibility of Van Dijk making the much travelled route from Southampton to Liverpool.
Although the Saints had not felt the full effect of the poaching of their best players - not just from Liverpool - until last season, Van Dijk was the last straw and that is why Saturday's clash is anything but a routine Premier League fixture.
On the surface all that is up for grabs is three points, but with Mane, Lallana, Lovren and van Dijk all expected to be named in their respective matchday squad, there is more than meets the eye with this clash.
The Southampton hierarchy will be undoubtedly be desperate to pull a fast one on Liverpool - like they did in the League Cup semi-final last season - but Liverpool too will be conscious of offering Van Dijk an insight into the set-up he was informed about, and still potentially has a chance to join.
It is set to be a edgy affair which transcends from the pitch and into the stands, as Liverpool fans will be keeping a keen eye over Van Dijk as he lines-up against their formidable attacking line, whilst the Saints faithful are likely to continue their own tradition of booing their former players.
With all their recent history off the field, the 107th meeting between Liverpool and Southampton on the weekend is set to be so much than it appears to be on the surface.