While the Cottagers cruised to victory at Crystal Palace in their Boxing Day fixture, Saints slumped to another top-flight defeat despite a change of management just before the World Cup break.
Match preview
Not for the first time, Fulham talisman Aleksandar Mitrovic was central to gaining three valuable points for his club on Monday, when Marco Silva's side put London rivals Crystal Palace to the sword at Selhurst Park.
However, it was the Serbian striker's two assists in a 'Man of the Match' performance which most caught the eye, as the visitors took advantage of a sluggish Palace team that ended the game with just nine men.
Having set up strikes for Bobby Decordova-Reid and captain Tim Ream - the latter a clinical half-volley on the turn - Mitrovic later nodded home his 10th Premier League goal since returning to the top tier in August.
His seamless adaptation mirrors that of his teammates at Craven Cottage this term, as Fulham have claimed a place in the top half of the table - partly by virtue of an away record which matches Chelsea's and surpasses that of Liverpool.
Victory on Boxing Day also ensured a bright start to the second phase of a unique campaign, after losing to both Manchester clubs in the space of a week just before all eyes turned to Qatar. Now, they end a successful year with a relatively kind home fixture, against the league's bottom club.
While Fulham have filled their boots by scoring 27 times in the Premier League so far, the root of Southampton's struggles has been a paltry return of just 13 goals.
Given such a lack of bite in the final third, and a gradual ebbing away of momentum behind his management of the South Coast club, Ralph Hasenhuttl made way for former Luton Town boss Nathan Jones last month - but the latter's top-flight debut certainly did not go to plan on Boxing Day.
Days after overcoming Lincoln City in the EFL Cup, Saints found themselves two goals down at the interval against Brighton, and despite James Ward-Prowse's goal midway through the second half they were consigned to a 3-1 home defeat.
As a result, Southampton have lost each of their last four Premier League fixtures, and they now visit a venue where they have won only once in their last 16 league visits - and not at all since 2014.
With his side sitting 20th approaching the new year, Jones certainly has his work cut out to help them avoid the drop, yet they are still only two points adrift of safety amid a congested bottom half of the table.
Any chance of leapfrogging others to escape the bottom three before 2023 kicks off rests on Saints winning their final match of a calendar year for the first time since 2011 - and Fulham are unlikely to prove accommodating hosts in that regard.
Fulham Premier League form:
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Fulham form (all competitions):
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Southampton Premier League form:
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Southampton form (all competitions):
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Team News
Following a comprehensive win earlier this week, Marco Silva is likely to field a settled side on Saturday, spearheaded by star striker Aleksandar Mitrovic.
The latter shook off a foot problem to feature on Boxing Day, and should again be supported by Willian, Andreas Pereira and Bobby Decordova-Reid.
Due to injury, Neeskens Kebano, Layvin Kurzawa and Manor Solomon all remain out of contention for the hosts.
Southampton, meanwhile, could be without Theo Walcott, who has been sidelined by a calf problem, while Tino Livramento remains on the long road to a return from his ACL injury. Midfielder Romeo Lavia (hamstring), defender Juan Larios (groin) and goalkeeper Alex McCarthy (ankle) are also on the sidelines.
Armel Bella-Kotchap is short of match-sharpness but may be promoted from the bench this weekend, in order to bolster a faltering back line.
Teenage winger Samuel Edozie will hope to keep his place in the visitors' lineup after making a big impression against Brighton in his first Premier League start for the club.
Fulham possible starting lineup:
Leno; Tete, Diop, Ream, Robinson; Reed, Palhinha; Decordova-Reid, Pereira, Willian; Mitrovic
Southampton possible starting lineup:
Bazunu; Walker-Peters, Lyanco, Bella-Kotchap, Perraud; Ward-Prowse, Diallo; Djenepo, Elyounoussi, Edozie; Adams