By Chris Harris at Emirates Stadium
Santi Cazorla’s stoppage-time penalty snatched three points for Arsenal to get their home campaign up and running.
Arsene Wenger's side faced an uphill task when Petr Cech inadvertently gave the Saints the lead, brilliantly tipping Dusan Tadic’s free-kick onto the bar only for the rebound to hit him on the back and bounce in.
Laurent Koscielny came to the rescue, marking his birthday with a stunning overhead kick.
Driven on by Francis Coquelin, Arsenal made the running in the second half, but the closest they went was a shot from Alexis that whistled just over the bar.
That was until the dying seconds, when Olivier Giroud was hauled down by Jose Fonte and Cazorla kept his nerve to beat Fraser Forster.
It was just enough to end Southampton’s resistance - and make it two straight wins in the Premier League.
SETTING THE SCENE
A week after watching some old favourites grace the Emirates turf, Arsenal’s fans had new heroes to hail.
Instead of Kanu, Robert Pires et al, it was Mustafi and Lucas who took centre stage as Premier League football resumed after the international break.
Lucas was one of three changes - Coquelin also came into the side - and one of two birthday boys - captain Koscielny also had that honour.
Granit Xhaka dropped to the bench alongside Alexis and the fit-again Alex Iwobi, as Wenger kept something in reserve for the opening Champions League game in Paris on Tuesday.
The Arsenal manager was in his thirties when Arsenal last lost at home to Southampton but the Saints arrived here looking for a fourth straight clean sheet in this fixture.
Teeming rain in north London saw the floodlights deployed earlier than usual. The spotlight, meanwhile, was trained on those two Arsenal debutants.
Mustafi was busier in the early stages as Arsenal struggled to find the fluency of their win at Watford.
Southampton had no such problems. Tadic and Steven Davis pulled the strings in midfield and Nathan Redmond buzzed around the edge of the area looking for openings.
He was the source of the opening goal, drawing a foul from Nacho Monreal to earn a free-kick on the edge of the box. Tadic floated one over the wall and luck deserted Cech, who tipped the ball onto the bar only for the rebound to hit his back and go in.
Arsenal were struggling to get their own creative players on the ball - especially Santi Cazorla - but the Spaniard did pick out Theo Walcott from a corner. His near-post header went over.
Mustafi endeared himself to the home fans with a strong challenge and a charge down the right. It helped Arsenal emerge from their torpor and they began to apply pressure as a team, Ozil setting up a chance for Monreal which Virgil van Dijk hacked clear.
The resulting corner brought the goal Arsenal wanted - and what a goal.
Coquelin jumped for the initial header, Lucas got enough on the second aerial challenge to send the ball towards Koscielny and he executed a perfect overhead kick to beat Forster. You don’t see many centre backs do that.
After that anxious start, the momentum was with Arsenal.
Walcott found Ozil on the edge of the box following a quick break, but for once the German’s touch let him down. Ozil turned provider next, picking out Lucas only for a defender to block his shot.
Southampton played on the break and only a perfectly-timed sliding interception from the covering Cazorla denied Redmond a clear route to goal.
Bellerin fizzed a shot just wide after cute build-up play involving Coquelin, Lucas and Ozil. And then it was time for a change - or two. Off came Lucas and Oxlade-Chamberlain; on came Olivier Giroud and Alexis.
A storming run from the excellent Coquelin set up Alexis for a run and shot that flew just over, and Monreal saw his low shot take a deflection and roll wide.
Arsenal nerves were fraying when Pierre-Emile Hojbjerg’s shot hit a defender and forced Cech into a fine save, and the keeper got back to kick away Shane Long’s follow-up.
Giroud steered a header into the side-netting from Cazorla’s precise chip, and that seemed to be that.
Then Fonte tugged at Giroud’s shirt and Cazorla waited patiently for Koscielny to receive treatment before applying the coup de grace.
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Referee: Robert Madley
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