Danny Welbeck then put the Gunners ahead after cutting inside and firing a right-footed shot that flew off the back of left-back Maya Yoshida and past keeper Alex McCarthy to put the home side 2-1 up seven minutes before the interval.
The second-half started with a poor performance from the hosts, which saw Southampton pressing Arsenal to get the equalizer and managed to do so in the 73rd minute through Charlie Austin.
Welbeck scored a late victor for Arsenal to inflict more misery on Mark Hughes' Southampton side.
Arsenal were misfiring until Aubameyang started and finished a flowing move with a deft finish past the onrushing Alex McCarthy following Welbeck's inventive flick - the Gabon striker having now scored six goals in his first eight league games.
The England forward had not scored a single league goal since September previous year, but proved the catalyst for a much-changed Arsenal side ahead of their Europa League quarter-final second leg at CSKA Moscow on Thursday.
The Gunners have a 4-1 advantage from the first leg.More news: Apple is developing touchless controls and curved screens for future iPhones
It is just one win in 19 league matches now and they have conceded six goals in two league games since Hughes replaced the sacked Mauricio Pellegrino in the middle of March. He did not give the Southampton defenders any time whatsoever and had a hand in all of Arsenal's goals.
- Danny Welbeck both scored and assisted in a Premier League match for the first time since September (v Bournemouth), which was also the last time he netted a league goal.
He'd get his goal in the 81st minute, stabbing home a header at the back post from an Iwobi cross.
Saints' chances were limited, but Elneny had to be on hand to clear off the line as Wesley Hoedt sent a header towards goal with Cech scrambling to tip a Long header behind soon after.
"Going into the Europa League on Thursday, it's going to be a hard tie even though we won the home game [4-1]".
- Mark Hughes has now lost each of his 11 trips to Arsenal in the Premier League, only Harry Redknapp against Manchester United (15) is on a longer wait for an away win against an opponent in the competition.
"People were questioning, will he come back or not?"