Stuart Armstrong volleyed Ralph Hasenhuttl’s Saints ahead after just three minutes at St Mary’s, but Pepe equalised five minutes later, Saka struck before half-time and Lacazette scored after the break to complete the turnaround and secure a key Premier League victory for Mikel Arteta.
The game started at a blistering pace: Alex McCarthy made a fine one-on-one save to deny Lacazette in the first minute, and Saints made the Gunners pay right away as Armstrong finished well off a James Ward-Prowse corner after three minutes.
Arsenal did not dwell on those early setbacks though, and Pepe pulled the visitors level with a clinical effort off a defence-splitting pass from Granit Xhaka five minutes later.
The pace was unrelenting as both sides had chances, but it was Arsenal who went ahead six minutes before half-time. Lacazette made amends for his early miss by slotting Saka through, and it was McCarthy’s turn to make an error - he raced out of his box but failed to close down Saka, who rounded the 'keeper and tucked the ball into an empty net.
Southampton looked for a route back into the game, but Arsenal struck after Emile Smith Rowe departing with an injury. The impressive Cedric Soares played a great cross-field ball to Saka, whose pinpoint cross was turned in from close range by Lacazette.
The victory sends Arsenal eighth - for the time being, at least - and will give the Gunners hope that European football, and potentiall even Champions League qualification, is not yet beyond them this season.