Both sides played out 2-2 draws just before the international break, with the Saints rescuing a point against Newcastle United while West Ham were pegged back by Crystal Palace.
The 21-year-old striker transferred to the Championship outfit for a reported £1.5million fee after scoring just four goals in 32 Premier League appearances for Ralph Hasenhuttl’s side.
Steve Bruce’s side go into the game after being knocked out of the EFL Cup on penalties by Burnley, while the Saints put eight unanswered goals past Newport County in round two.
The emphatic victory helped them to reach the third round of the 2021/2022 League Cup.
The first match in front of a full St. Mary´s crowd in almost 18 months also saw these sides meet for the first time since Ralph Hasenhuttl´s men conceded nine goals without reply at Old Trafford in February.
The Red Devils opened their campaign with a 5-1 home victory over Leeds United last weekend, while Southampton suffered a 3-1 defeat to Everton at Goodison Park in their first game of the season.
Mowbray had been open about his interest in the Southampton player, following Adam Armstrong’s £15 million (€17m) move to St. Mary’s.
The Spaniard, famous for a rather more high-profile comeback with the red half of the city in 2005, has plenty of work to convince the doubters he can ever be accepted at Goodison Park, but this was as good an opening as he could have wished for.
The Toffees will seek to sustain a European charge this term, while Southampton will aim to condemn the second half of their 2020-21 season to history.
Obafemi is under contract with the Saints until the end of this season but due to injury and loss of form he has been unable to establish himself at Southampton, making just four Premier League appearances as sub last season.
Opportunities for the striker under Thomas Tuchel were few and far between last season, leading to speculation that he could be sold ahead of the 2021-22 season.
The 31-year-old, who won 19 international caps between 2012 and 2017 and travelled to Euro 2016, has signed a two-year contract with Brendan Rodgers’ Foxes.
The Cottagers’ fate was confirmed with defeat at home to Burnley on Monday, while Southampton beat Crystal Palace last time out to climb up to 14th place.
The Reds have won just one of their last five games in all competitions, drawing the last three in succession, and they face a Saints side who are looking to complete the league double against them for just the third time in their history, previously doing so in 1960-61 and 2003-04.
The Saints had Jannick Vestergaard sent off early on, but managed to take a shock lead in the second half.
The clause was inserted in the deal that took him to the Foxes in 2017 and after struggling to find his feet, the 24-year-old is presently one of the hottest strikers in the English Premier League.
Iheanacho has 14 goals in 30 appearances for the Foxes this season, having netted 10 last term and just two in 2018-19.
The striker went 12 months without scoring but is now looking to fire the Foxes to the FA Cup final.
Ralph Hasenhuttl’s side moved 10 points clear of the relegation zone with eight games left after a dramatic fightback at St Mary’s.
The Clarets, meanwhile, are looking to secure back-to-back away league wins for the first time since July 2020.