After Grzegorz Rasiak netted his third goal in three successive games against the Pilgrims, the Saints were made to mount a stern rearguard action.
Raisak's fifth minute strike, which came when he pounced upon goalkeeper Romain Larrieu's poor kick, was clouded in controversy after he had been standing in an offside position earlier in the build up.
However, Argyle, who were missing six first-team regulars through injury, bounced back impressively and deserved their equaliser just after the hour when skipper Barry Hayles netted his eighth goal of the season.
Hayles was later sent off for a second yellow card - given for handball after closing down goalkeeper Kelvin Davis' clearance - but Argyle had done enough to thoroughly deserve their share of the spoils.
The Pilgrims might even have won the game late on when David Norris rammed home a loose ball after Akos Buzsaky's shot had been beaten out by Davis.
Argyle's injury problems meant they were forced to give full debuts to striker Cherno Samba and 16-year-old midfielder Dan Gosling.
Samba should have scored in the opening moments but Davis saved his half-hit shot, and after Rasiak's strike, Lilian Nalis' header and a shot from Gosling were cleared from the goalline by Jermaine Wright and Gareth Bale respectively.
Chris Baird made a superb block to thwart Buzsaky and the same player then saw a shot stopped by Davis, who also performed well to beat out an opportunity that fell to Gary Sawyer.
Sawyer was outstanding in defence, denying Bradley Wright-Phillips on two occasions as Southampton looked to sew the game up on the counter attack.
Despite losing Hayles, Argyle strove for the winner that their tireless effort and self-belief arguably merited but they found Southampton too determined to break down again.