Kicking off 24 hours before their title rivals, Arsene Wenger's side were unable to keep up the pressure on Manchester City and Chelsea as they blew what had been an impressive second-half comeback.
They were forced to settle for a point in a hard-fought 2-2 draw that ended a five-match winning streak, which means they could be usurped at the top of the standings on Wednesday.
It could have been even worse for the Gunners as they were fortunate to go in at half-time just a goal behind to a Southampton side performing impressively despite the continuing off-field headlines.
Jose Fonte has been caught up in many of those, having been on the receiving end of Dani Osvaldo's fit of rage in training, but was quick to thank the home fans on his first start since the incident as he headed Saints ahead and celebrated by beating the club badge passionately.
Sam Gallagher, making his full debut at the age of 18, should have doubled the hosts' advantage soon after when a Nacho Monreal clearance fell fortuitously into his path, allowing the Gunners to turn the match on its head at the start of the second half.
Just three minutes after the restart, Bacary Sagna met an over-hit cross on the right flank and struck a low goalbound strike, credited to Olivier Giroud thanks to the faintest of touches.
It was the Frenchman's fourth goal in five matches in all competitions - a record Santi Cazorla bettered in the 52nd minute with a fine strike from the edge of the box to make it five in five.
The hosts would not lie down, though, and showed impressive resolve to strike back within two minutes, as Adam Lallana fired home a Jay Rodriguez cutback to make Saints just the second side to score more than one against Arsenal in their last 22 league games.
Wenger's men do not have the joint-best away record in the top flight for no reason, though, and came close to going back in front when a Mesut Ozil shot deflected off Fonte and looped on to the crossbar.
However, hopes of eking a late victory took a major blow as Mathieu Flamini was deservedly handed a straight red card for a two-footed lunge on Morgan Schneiderlin, meaning Arsenal had to weather the storm in the closing stages.