Southampton returned to the Premier League for season 2012–13 initially under Nigel Adkins. Substantial sums were spent to strengthen the playing squad, but early in the season, Adkins was replaced by Argentine coach Mauricio Pochettino. Southampton finished the season in 14th place, and next season in 8th.
At the end of the 2013–14 season, Pochettino departed the club for Tottenham. The club subsequently appointed Ronald Koeman as his replacement on a three-year contract, and made several high-profile sales over the summer. In the final game of the 2014–15 season, a 6–1 victory against Aston Villa, Sadio Mané scored three goals in the space of 176 seconds, the fastest hat-trick in the history of the Premier League. The club finished seventh, then their highest ever Premier League rank, therefore qualifying for the 2015–16 UEFA Europa League.[citation needed] After defeating Vitesse, the Saints were eliminated in the play-off by Midtjylland. The following season, Southampton once again set new records for the club at the end of the season, finishing in sixth place. They once again qualified for the Europa League, although this time immediately entered the group stages, as opposed to the play-off rounds.
In June 2016, Koeman left Southampton to join Everton and Claude Puel replaced him on a three-year contract. The club were eliminated in the group stage of the Europa League but were more successful in the EFL Cup, where they lost 3–2 in the final to Manchester United. The club ended the 2016–17 season in eighth. During the summer, Puel was replaced as manager by Argentine coach Mauricio Pellegrino, previously of Deportivo Alavés. In mid-season, the club sold Dutch defender Virgil van Dijk to Liverpool for an estimated £75 million, Southampton's record sale and a world record for his position. Pellegrino was sacked in March 2018 with the team 1 point above the relegation zone, and his replacement, former player, Mark Hughes, guided the club to a 17th-place finish, avoiding relegation on the last day of the season. Hughes signed a new contract at the end of the season but a poor start to the following season led to him being sacked in December 2018 with the team in 18th place. He was replaced with former RB Leipzig boss Ralph Hasenhüttl, who steered the club away from relegation to finish 16th.
In August 2017, Southampton Football Club confirmed that the Chinese businessman Gao Jisheng had completed a multimillion-pound takeover of the club, acquiring an 80% stake for around £210m after successfully passing the relevant checks, including the Premier League's owners and directors test. The deal followed more than 12 months of talks between the Gao family and the South Coast club. The investment was made personally by Gao and his daughter Nelly as opposed to being sanctioned through Lander Sports, as originally mooted. Hangzhou-based Lander is the family's business arm, which develops, constructs and manages sports sites.
Southampton suffered their worst ever defeat on 25 October 2019, losing 9–0 to Leicester City at home, this would later be replicated on 2 February 2021 against Manchester United at Old Trafford in the following campaign, albeit under different circumstances. It is tied with Ipswich Town's defeat by Manchester United in 1995 as the biggest defeat since the Premier League's inception. Following universal backlash toward the team's performance, the players and coaching staff refused their wages from the match and instead donated them to the Saints Foundation. On 9 April 2020, Southampton became the first Premier League club to defer players salaries, during the COVID-19 pandemic. Southampton stated that manager Ralph Hasenhüttl signed a four-year contract extension on 2 June 2020 until 2024. Despite a poor start that saw them in the relegation zone as late as November, Southampton improved greatly as the season went on, ending the year with a seven-game unbeaten streak to finish 11th in the league. Their final tally of 52 points was the team's highest total since 2015–16. This strong finish led to Hasenhüttl being named Manager of the Month for July 2020.
The club's good run continued in the 2020–21 season with the Saints sitting in third after 13 games. The team also had a successful run in the FA Cup where they reached the semi-finals, losing to eventual winners Leicester City. In November, Southampton briefly led the Premier League table. However, despite the outstanding start to the season, a mid-season loss of form and an accumulation of injuries which decimated the senior squad ranks, due in part to the unavailability of much of the club's training facilities resulting from the restrictions imposed during the second lockdown in England. As a consequence of this, Hasenhüttl was forced to field many of the club's youth players in an attempt to fill in the gaps in his senior squad. After an impressive run during the first half of the season, Southampton would eventually finish in 15th place.
In January 2022, Chinese national Gao Jisheng sold his 80% stake in Southampton F.C. to a group called Sport Republic financed by Serbian national Dragan Šolak for £100m, reflecting a £110m loss on Jisheng's investment made in the club in 2017. Despite most pundits predicting them to be relegated at the start of the season, Southampton finished the 2021–22 season in 15th place for the second consecutive year.