Second-half goals from Kai Havertz and Gabriel Martinelli turned the tide after Cameron Archer shocked the hosts with an early second-half strike for the visitors.
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Bukayo Saka sealed the win with a late goal, ensuring Arsenal became just the second Premier League club to reach 400 home victories.
Despite dominating the first half, Arsenal went into the break frustrated as Southampton held firm. However, Archer broke the deadlock 10 minutes after the restart, finishing neatly on a counter-attack after Raheem Sterling, making his first league start for Arsenal, was dispossessed by Mateus Fernandes.
The setback ignited a response from the Gunners, as Havertz equalized with a fine finish three minutes later, followed by Martinelli’s well-timed header from a Saka cross.
Southampton fought back, hitting the woodwork twice through Dibling and Adam Armstrong, but Saka capped off his stellar performance with a clinical finish to secure the three points.
The win keeps Arsenal within a point of league leaders Liverpool going into the international break, while Southampton remain winless with just one point from seven games.
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