Southampton were seconds away from picking up their third draw of the season, until referee Bobby Madley awarded a late spot-kick to the Gunners.
DuÜan Tadić's free-kick found the back of the net via the crossbar and the back of Petr Cech after just 18 minutes, before Laurent Koscielny hit back with a stunning overhead kick.
With the game ebbing towards shared points, Olivier Giroud went down under pressure from JosÚ Fonte in controversial circumstances. The penalty was awarded and Santi Cazorla duly converted to claim all three points for the hosts.
Claude Puel handed a first start of the season to Ryan Bertrand, fit again and available for selection after a spell on the sideline with an injury. Steven Davis partnered Jordy Clasie in midfield, with Nathan Redmond joined in attack by Jay Rodriguez.
The Saints started strongly, pinning back the hosts and repeatedly launching attacks after seizing possession. Rodriguez went close with a headed effort, before Tadić made the breakthrough soon after.
The Serbian took advantage from 20 yards after Redmond was fouled by Nacho Monreal, sending his strike into the back of the net after seeing it bounce down from the crossbar and over the line after hitting the back of Cech in the Arsenal goal.
Saints pushed for a second goal, but were cruelly stung when Koscielny produced an unthinkable overhead kick to level the scores.
Shane Long replaced Rodriguez at the break, and went closest to finding a second goal when he chipped just wide of Cech's far post after getting one-on-one with the former Chelsea shot-stopper.
Saints were made to pay for missed opportunities deep in added time when Cazorla dispatched a late spot-kick, after skipper Fonte was adjudged to have fouled Giroud.
There were plenty of protests from the visiting bench and supporters, with Koscielny down with a head injury when the ball was put into the box, and with the penalty award coming just seconds after Long was fouled at the other end of the pitch.
It ended 2-1 at Emirates Stadium and Saints found themselves slipping into the relegation zone at the close of play.
SAINTS: Forster; CÚdric, Fonte, Van Dijk, Bertrand; Romeu; Clasie (H°jbjerg - 64'), Davis; Tadić (Ward-Prowse - 80'); Redmond, Rodriguez (Long - 46').
Unused Subs: McCarthy, Yoshida, Targett, Austin.