Southampton were unable to build on Stuart Armstrong’s early goal as visitors Arsenal fought back to earn three points at St Mary’s.
Armstrong controlled a tricky half-volley from James Ward-Prowse’s third-minute corner to break the deadlock, but the lead would prove short-lived as Nicolas Pépé equalised five minutes later.
Arsenal went in at half-time in front after star man Bukayo Saka raced on to Alexandre Lacazette’s pass to round Alex McCarthy, before crossing low for the Frenchman to complete the scoring 18 minutes from time.
With Kyle Walker-Peters injured and Ryan Bertrand suspended, Ralph Hasenhüttl was forced into changes in both full-back positions.
Enter Academy graduates Yan Valery and Jake Vokins, who were both making their first Premier League starts of the season.
Hasenhüttl’s only other alteration was to recall McCarthy in goal, who returned to make his 100th Southampton appearance on a night of milestones for the club.
There was a breathless start to proceedings as Arsenal threatened to take the lead inside 60 seconds, before falling behind and drawing level, all in the first eight minutes.
First up, Lacazette was put clean through on goal by Granit Xhaka, but could not beat Saints’ newest centurion, who spread himself smartly to keep him out.
The hosts responded with a first run and cross from Valery into Danny Ings, whose header at the near post was deflected wide.
Trotting across to take it was, of course, the skipper, who duly celebrated the occasion of his 300th game for the club with a pinpoint corner brilliantly dispatched by Armstrong, connecting on the half-volley to guide the ball high past Bernd Leno’s left hand and into the corner of the net from 15 yards.
Back came Arsenal. Shortly after Saka showcased his threat with a quick dart to the byeline, the Gunners found an equaliser when Thomas Partey found Pépé, who was able to take a touch, steady himself and angle a low shot across McCarthy to draw his team level.
Now a goal apiece, the action continued at electric pace. Theo Walcott dragged a shot wide with Valery in space to his right, while Vokins crossed for Ché Adams, whose thumping header was thwarted by the flying figure of Leno.
Saints’ young full-backs were heavily involved. Valery surged into the box, checked inside and shot wide on his left foot, but clearly was not short on self-belief to go alone.
Armstrong then went close to a second, cutting in from the left and curling the ball fractionally wide, as Hasenhüttl’s side began to wrestle back control after Arsenal had enjoyed a good spell, featuring an eye-catching volley from Cédric that just veered away from the target.
Saints were creating chances but were being prised open rather too freely by an Arsenal side transformed from the one they faced in the FA Cup on Saturday, and at the Emirates in December.
That proved the case again when Lacazette’s first-time pass on the turn split the hosts, inviting Saka to run in behind Vokins, beat the onrushing McCarthy in a race to the ball and keep his cool to slide the ball into the unguarded net.
Trailing at the interval, Saints took the game to the visitors in a bid to get back on terms.
Walcott again used Valery as a decoy, this time shooting with more conviction but too close to Leno, before Vokins sent in a teasing cross that was just missing a finishing touch.
But at the other end, the youngster was being given a stern examination by England starlet Saka, who was Arsenal’s most dangerous weapon, this time stepping inside and firing wide as he looked to add to his tally.
Saints kept pushing, as the well-marshalled Ings tiptoed his way into the box only to run out of room, with Arsenal doing a good job of restricting clear sights of goal.
Hasenhüttl, perhaps concerned by the influence of Saka down that side, chose to withdraw Vokins midway through the second half, as Nathan Redmond came on to the wing, Armstrong moved inside and Ibrahima Diallo filled the void at left-back.
But five minutes later Arsenal had the killer third with Saka the architect, crossing low for Lacazette to slide in the clincher from close range.
Hasenhüttl again turned to his bench, opting for the energy of young legs in Dan Nlundulu and Caleb Watts, the latter for his Premier League debut.
But clear opportunities, unlike in the first half, were proving elusive. Ward-Prowse lined up a free-kick seven minutes from time that would have offered hope, but Leno was up to the task, and it would prove third time lucky for Arsenal against Saints this season.