Southampton were unable to build on a bright start at the Emirates Stadium, as Arsenal ran out comfortable winners after two quick-fire first-half goals.
Alexandre Lacazette broke the deadlock against the run of play at the end of an electrifying counter-attack, before Martin Ødegaard crucially doubled the lead six minutes later.
Saints’ fate looked sealed with just 26 minutes on the clock, and Arsenal might have added more than just one goal after the interval, scored by Gabriel on the hour.
The Brazilian defender had only just seen one chalked off for offside, while namesake Martinelli and Bukayo Saka rattled either post in the quest for a fourth goal that never arrived.
Ralph Hasenhüttl made five changes to his starting line-up, four of which were forced on him through injury and suspension.
With Alex McCarthy and Fraser Forster both sidelined by injury, there was a debut for Willy Caballero in goal, while at the top end of the pitch Ché Adams missed out with a muscle strain.
Mohammed Salisu and Oriol Romeu were both suspended, having picked up fifth yellow cards of the season against Brighton.
That meant a return for Jack Stephens after three months out of action, while Ibrahima Diallo partnered James Ward-Prowse in midfield and Adam Armstrong replaced Adams.
The only alteration made through choice was to restore Jan Bednarek to the backline, with Lyanco dropping to the bench.
Saints actually started the game in encouraging fashion, but only after they were indebted to the honesty of Saka, who stayed on his feet when caught in the box.
After that the visitors settled into their task. Space opened up for Nathan Tella to drive at the Arsenal defence, but his shot was scuffed into the arms of Aaron Ramsdale.
Armstrong then found himself in a similar situation, but his shot was deflected off target.
Saints are still waiting for a James Ward-Prowse free-kick goal this season, but twice the skipper threatened to break his duck as Saints continued on the front foot.
First he sent Ramsdale scrambling to his right, pushing the ball behind for a corner, before a second opportunity presented itself right on the 18-yard line – too close, if anything, as Ward-Prowse went for power to the side of the wall but cleared the crossbar.
Arsenal were yet to threaten, but suddenly burst into life with a quite brilliant opening goal.
Saints pressed from the front, but a sequence of first-time passes carved them open, freeing Saka down the right flank, and the England man squared the ball across goal for Lacazette to lash home the opener.
Six minutes later, the home team were almost out of sight. Kieran Tierney found himself alone at the far post, and, despite making a mess of his first cross, was afforded another chance to deliver, this time deflecting off Tino Livramento.
When the ball looped into the air, Tierney headed it back across goal and Ødegaard was in the right place to head home from six yards, as once again Caballero was given no chance on his first professional appearance in 15 months.
Still Arsenal wanted more. Lacazette twice escaped the Saints defence before crucial interceptions halted him in his tracks, latterly from the flying figure of Kyle Walker-Peters.
Things went from bad to worse for Hasenhüttl when Armstrong hobbled off before half time, replaced by Mohamed Elyounoussi, as Saints’ injury problems worsened.
Tella provided some brief optimism for the travelling fans early in the second period, testing Ramsdale with a low shot parried into the danger zone, but there was no teammate on hand to mop up the rebound.
Then Tella got in behind Gabriel, already booked early in the game, who seemed to drag him down, but the referee saw it differently, judging both players were equally guilty.
The defender might have been dismissed on another day, but was in the right place to force the ball home from a corner, only to be denied by the offside flag.
The Brazilian would not be kept at bay for much longer, though, as he soared above Caballero to head in Arsenal’s very next corner.
The Gunners were in no mood to stop there, as Gabriel Martinelli curled an effort against the post before Walker-Peters threw himself in the way of another shot on the follow-up.
Next to go close was Saka, who rattled the woodwork himself soon after, as Saints hung on to prevent an even more one-sided scoreline.
Hasenhüttl’s response was to sacrifice one of his attacking players, withdrawing Armando Broja and introducing Lyanco to give Saints some more stability.
Nathan Redmond and Tella kept Ramsdale busy, as the keeper made two more impressive stops to keep his clean sheet intact, but more concerning were the issues at the other end.