The visitors resembled a rabbit in the headlights for most of the first half at Emirates Stadium as they failed to deal with Arsenal's pace and directness - epitomised as early as the 11th minute as Jos Hooiveld accidentally put into his own net.
Lukas Podolski bent in a 25-yard free-kick as the onslaught continued, before Gervinho rifled home and Nathaniel Clyne netted an own goal to make it 4-0 inside 37 minutes.
Wojciech Szczesny's clanger denied the north Londoners a fourth successive clean sheet to start the season as the returning Poland international flapped at a cross late in the first half and Danny Fox lashed home.
It proved a mere consolation, though, as Gervinho and former Southampton winger Theo Walcott netted in a more even second period to condemn Nigel Adkins' side to a fourth league defeat.
Arsenal made three changes coming into the game, with Szczesny the standout returnee after missing recent matches with a rib injury.
Saints, meanwhile, stuck with the same starting team that fell to a harsh 3-2 defeat to Manchester United before the international break, while new signings Gaston Ramirez and Maya Yoshida were named on the bench.
The latter was brought in to shore up a weak Southampton defence that found itself under pressure from the outset in north London.
Podolski tested Kelvin Davis with a stinging effort inside three minutes, before former Southampton winger Alex Oxlade-Chamberlain's dangerous cross was inexplicably scooped over the bar by Santi Cazorla.
The early pressure continued as Southampton regularly gave away possession as they failed in their attempts to get a foothold on proceedings.
Arsenal capitalised on the visitors' early ineptitude as Podolski took possession in the middle and played through Kieran Gibbs, whose low effort squirmed through Davis' legs and was inadvertently turned home by Hooiveld.
The hosts' dominance continued after the 11th-minute opener and came close to doubling their advantage soon after.
Davis flapped at a Cazorla corner and had to be on his toes to prevent Per Mertesacker heading home when the ball was played back into the box.
Gervinho was the next to threaten, nodding wide and then bursting forward to send a driven effort just wide of the right-hand post.
The early exchanges made bleak viewing for the travelling fans and Adkins was forced into his first change after 28 minutes, bringing on Yoshida for his debut in place of Hooiveld, who had been struggling with a calf injury this week.
The Japan defender could do nothing, though, to prevent Podolski scoring three minutes later.
After Coquelin was upended, the Germany international exquisitely curled a 25-yard free-kick over the wall into the top corner past the helpless Davis.
However, the Southampton goalkeeper - and defence - should have done much better with Arsenal's third that came after 35 minutes.
Gervinho connected with an excellent Mikel Arteta dink over the top and the Ivorian lashed home, finding time and space to beat Davis at his near post.
It was proving a nightmare first half for Saints as they failed to cope with Arsenal and it got worse eight minutes before half-time with a second own goal.
Another break ended with the being ball played out left to Gibbs, who again saw his cross directed home by a player in yellow - this time Clyne the unfortunate party.
It was not just Southampton making errors, though, as the returning Szczesny spilt a high cross from the right under pressure from Rickie Lambert, allowing Fox to lash home on the stroke of half-time.
It was one of a handful of chances for the visitors in the second half, leading Adkins to bring on record signing Ramirez for his debut in a bid to create more going forward.
Saints looked far more confident and composed following the introduction of the Uruguay international, who tested Szczesny five minutes after coming on.
Ramirez soon turned provider as he played through Lambert, but he could only direct wide under pressure.
Oxlade-Chamberlain bundled wide a Gervinho cross as Arsenal looked to extend their advantage - which they managed to do in the 71st minute.
Cazorla, impressing once again in midfield, played through substitute Aaron Ramsey, whose exquisite turn was followed up by a shot that came back off the post for Gervinho to tap home.
Davis was forced into a fine save to prevent former team-mate Oxlade-Chamberlain netting, before substitute Walcott capped a fine day for Arsenal by netting late on after the Saints goalkeeper parried.