As the newly appointed Saints boss Will Still watched on from the stands, his goalkeeper, Aaron Ramsdale denied his former employers Arsenal the lead inside two minutes, saving Gabriel Martinelli’s header well.
Mikel Merino came closer to scoring midway through the first half, clipping the crossbar with a header of his own as Martinelli turned provider. Thomas Partey’s long-range strike also had to be held by Ramsdale, while he also made a brilliant save to deny Martinelli one-on-one.
The Gunners finally made the breakthrough just before HT, and there was not a much more popular scorer than Kieran Tierney, who tapped home Ben White’s cross on his final Arsenal appearance. Southampton, like much of the season, were second best, but Kamaldeen Sulemana at least provided a threat on the counter.
Ethan Nwaneri tested Ramsdale early in the second half, before Jay Robinson forced David Raya into his first stop with a fierce near-post strike.
With a chance of winning the Golden Glove outright for the second successive season, the Spaniard would have been disappointed when Southampton equalised from the resulting corner. Ross Stewart rose highest to direct his header into the top corner for his first league goal this campaign, like fellow Scotsman Tierney.
It was Arsenal who pushed most for a winner in the latter stages, as Bukayo Saka headed home but in an offside position.
They did manage to find it just before stoppage time though, as Martin Odegaard fired brilliantly into the bottom corner from range.
Already-relegated Southampton suffered a record 30th defeat in a Premier League campaign as a result, while the Gunners won their 24th final-day top-flight match, the most of any team to do so.
Flashscore Man of the Match: Martin Odegaard (Arsenal)