Du Plessis (110 not out) defended resolutely in partnerships with AB de Villiers (33) and Jacques Kallis (46) after resuming at 77-4, before guiding the South Africans to 248-8 at stumps in a tense last hour of the second test at Adelaide.
Du Plessis batted for seven hours and faced 376 balls, sprinkling 14 boundaries into a gritty defensive knock to ensure back-to-back draws between Australia and South Africa in a series for the first time since 1921.
In the end, a late two-wicket burst from Peter Siddle (4-54) -- removing both Dale Steyn and Rory Kleinveldt for ducks -- left it up to Morne Morkel (8 not out) to navigate the final over.
The No. 10 batsman hit two boundaries in the last over to deprive the injury-depleted Australian attack a victory that most people had expected coming into the final day.
Du Plessis anchored an 89-run fifth-wicket stand with de Villiers and 90 for the sixth with Kallis, who was batting with a hamstring injury that has prevented him from bowling or fielding since early on day one and will likely rule him out of the third test in Perth starting Friday.
After no wickets fell in 35 hours in the first session, Siddle bowled de Villiers just after lunch to end his 220-ball innings -- the longest without a boundary in test records.
Kallis batted stubbornly for 2 ½ hours, facing 110 balls before he walked after giving a bat-pad catch off Nathan Lyon (3-49) to Ed Cowan at short leg, making the total 233-6 and exposing the South African tail.
Steyn batted for 36 minutes without scoring a run before he miscued a low full toss from Siddle directly to Rob Quiney to make the total 234-7 with a half hour to play, and Kleinveldt was bowled three overs from the end.
Australia had been on top of the game since winning the toss, deciding to bat and amassing 550 in the first innings -- including a whopping 482-5 on the opening day, a double century for Michael Clarke and hundreds for David Warner and Mike Hussey.
After a promising start in reply and a century by skipper Graeme Smith, the South Africans lost wickets in clusters -- around a rearguard partnership between du Plessis and Kallis -- to be all out for 388 and give up a 162-run lead.
Clarke declared midway through the penultimate day at 267-8, setting South Africa a victory target of 430 and giving his under strength bowling attack 4½ sessions to take 10 wickets.
Australia's push for a win started positively with Ben Hilfenhaus removing Smith (0) in the first over and Lyon picking up a pair to have the South Africans reeling at 45-4.
That's when South Africa gave up pursuing a record fourth-innings total win, and the stonewalling started.
The South African batsmen batted with resolute determination, blocking, prodding and fending off the attack in the gritty effort to force a draw and protect their No. 1 test ranking.
The pitch didn't deteriorate as much as expected and the Australian attack was missing fast bowler James Pattinson, who damaged ribs while bowling in the first innings and has been sidelined for the rest of the southern summer.
Siddle and Hilfenhaus had to take up the extra load on the last day while Clarke rotated offspinner Nathan Lyon with the part-time bowlers searching for a wicket.
The Australians had some chances -- du Plessis was given out twice for lbw to Clarke by umpire Billy Bowden but had the decisions overturned both times on review, then Wade wasn't able to glove a sharp chance for a caught-behind off Ben Hilfenhaus when he was standing up at the stumps in the over before the tea interval.
Kallis also played a loose drive on 6, with the total at 143-5, and Lyon wasn't able to reach the return catch, and Steyn had a life when Ed Cowan put down a difficult chance, at his ankles, at short leg off Siddle with 11 overs to go.
The 28-year-old du Plessis, given his test debut here after injured J.P. Duminey was ruled out of the series last week in Brisbane, made a well-compiled 78 in the first innings and proved his worth to the team with a valiant hundred in the second.
He held his nerve in a spell against Clarke that easily could have ended his innings if not for the decision review system, which allows each team two referrals to a TV umpire.
One was close, the ball pitching a fraction outside leg stump when he didn't offer a shot on 33; the other was a poor call from umpire Billy Bowden that didn't even hit him on the pad.
He survived a third review for lbw, this time by the Australians after Bowden gave him not to Lyon in the penultimate over of the morning session, when replays indicated the ball would have bounced over the stumps.
The South Africans need to avoid a series loss to retain the No. 1 ranking and are pushing for a second consecutive draw, while Australia needs to win to have any chance of reclaiming top spot.
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