Ponting had been hoping to sign off in his 168th test with a victory that would have allowed Australia to leapfrog the Proteas and return to the summit of the game they dominated for so much of his career.
Australia, 40-0 overnight, never looked getting anywhere near the winning target of 632 they had been set, however, and were bowled out for 322 in their second innings shortly before the scheduled close of play.
Appropriately, it was the South African bowling unit which sealed the victory after finally firing in Perth to turn the series around with a devastating spell on the morning of day two at the WACA.
The hosts had had the better of day one as well as the drawn tests in Brisbane and Adelaide but the South Africans struck back with a vengeance to become the first team since West Indies in the 1980s and 1990s to win consecutive series Down Under.
They got the best possible start to the day on Monday with two early wickets which brought 37-year-old Ponting to the crease for his 287th and final test innings.
Welcomed onto the field by a guard of honour of applauding South Africans, he lasted just 40 minutes and 23 balls before the same players were shaking his hand as he headed back to the pavilion with eight runs to his name.
Two fours, the first a vintage pull, closed his test tally at 13,378 runs for an average of 51.85 from 168 matches - the second highest run count in the long history of the game.
Spinner Robin Peterson (3-127) will go down in the record books as the last bowler to dismiss the Tasmanian, tempting Ponting into an attempted cut which ended up as an edge into the hands of Jacques Kallis in the slips.
The former Australian captain took off his helmet and raised his arms to accept the applause of the crowd before taking his leave from the field where he made his test debut 17 years ago.
Opener Warner (29) lasted just two deliveries in the bright morning sunshine before edging the ball to Graeme Smith in the slips off the bowling of Vernon Philander.
Watson (25) was the next to depart with Smith again taking the catch after Morne Morkel had softened the all-rounder up with some short bowling.
Ed Cowan outlasted Ponting and had just reached his half century when he fell for 53, leaving Michael Clarke and Mike Hussey to try and build the sort of partnership they enjoyed when Australia were in the ascendancy in the first two tests.
It was not to be, though, as Clarke (44) was stumped charging down the wicket to Peterson with Hussey (26) and Matthew Wade (10) soon following him back to the dressing room.
The tea break only delayed the departure of Mitchell Johnson (three) and John Hastings (20) but Mitchell Starc (68 not out) and Nathan Lyon wagged the tail with some vigour in a 10th wicket partnership of 87.
Starc showed his top order how they should have been done and claimed his maiden half century in 32 balls, scoring nine fours and two sixes in a fluent innings before Lyon was caught by Smith off the bowling of Dale Steyn (3-72).