The full-back claimed a point for his side with a rasping drive late on, cancelling out Gabriel Agbonlahor's first-half opener as the Villans' wait for a win goes on
Though the visiting side dictated the opening exchanges, it was the relegation-fearing Villans who struck the first blow to end the Saints' run of over seven hours without conceding a goal.
A hopeful long ball forward forced Fraser Forster to dash from his area but he was beaten to the ball by the electric pace of Gabriel Agbonlahor, who was able to finish into an unguarded net.
Southampton pushed forward in search of an equaliser and finally found it with time running out. Left-back Ryan Bertrand raced towards the byline and pulled the ball back for Clyne, fresh from making his England debut, who lashed a fierce shot past Brad Guzan as the spoils were shared.
Jores Okore made his first Villa appearance since September 2013 after a serious knee injury as part of three changes to Villa's back four, which was quickly put under siege by the visitors.
Southampton came into the game as one of the league's form sides after five straight wins in all competitions and went close three times in the opening 10 minutes as they looked to impose themselves on the contest.
The makeshift Villa defence stood firm, however, not allowing Southampton anything clear-cut, while Agbonlahor looked a menace on the counterattack despite a lack of support, with normal partner-in-crime Christian Benteke still serving a suspension.
And it was the Villa captain who duly managed to break the deadlock all by himself on the half-hour mark.
A heave out of the Villa defence should have been easily dealt with, but Toby Alderweireld left the ball for an indecisive Forster, allowing Agbonlahor to nip in and round the England goalkeeper before slotting into the net.
Sadio Mane drew a flying save out of Brad Guzan as Southampton were unable to even the scores before the interval and Ronald Koeman began the second half with Dusan Tadic closer to Graziano Pelle in an attempt to penetrate Villa's stubborn defence.
It did little to boost the visitors initially and they could not find a way into the heart of the stubborn Villa defence despite dominating possession.
Indeed, Villa should have doubled their advantage in the 78th minute. Andreas Weimann led a swift counterattack that resulted in Agbonlahor squaring for the Austrian 12 yards out, but he launched his shot high into the Holte End.
And he was made to pay just three minutes later, with England defender Clyne providing perhaps an unlikely source of inspiration as his scorching effort gave Guzan no chance.
The point only moves Villa up to 16th - though recent draws against two of the league's in-form sides will boost confidence - while Southampton's failure to win leaves Chelsea a dominant six points clear at the top of the Premier League table.