Captain AB de Villiers and Graeme Smith precursor (125 each) hit tons as South Africa made 312-4, but centuries from Kumar Sangakkara (102) led tourists 314-8 at the Wanderers and the second victory in three days.
Sri Lanka was cruising before Sangakkara was the fourth wicket to fall with 275 runs on board and later South Africa's rally saw them take two wickets in three balls in the last over.
She left the tourists need five runs with two balls to succeed and Robin Peterson hit Senanayake six snatch victory in an exciting culmination of a two-month tour.
Sangakkara hit 10 fours in the first ODI ton against South Africa and were also valuable contributions Lahiru Thirimanne (69), Upul Tharanga (46) and captain Tillakaratne Dilshan (41).
De Villiers and Smith excelled as South Africa recovered from a sluggish start early speed, having sent in to bat by Dilshan in the match delayed by rain for one hour at the beginning of the Sri Lankan innings.
De Villiers finished unbeaten after 98 before delivery, while Smith received a standing ovation from the sold-out crowd of 30,000 after caught in the middle of Dinesh Chandimal wicket Lasith Malinga bowling from.
While the Proteas skipper confirmed his status as one of the best players of stroke in the modern world with 10 fours and four sixes, Smith could not contain his joy when he left after the first ton of timely ODI three years.
There was a media and public outcry against him a week ago, after six innings, 28 and two in the first three games of the series, before he stopped to rot in a busy 68 in Kimberley two days ago.
Smith embroidered his innings with nine fours and four sixes from 143 balls in 203 minutes during the stand and the crowd reveled in the sun-drenched his change of fortune.
South Africa lost the knife Alviro Petersen (6) with only 10 runs on board and was 70-2 when the FAF du Plessis (24) left before De Villiers and Smith took on the responsibility.
Proteas was 133-2 after 30 overs and running speed of 4.43 needs to be improved on the right track batting, who captains past and present properly made with 44 runs coming during the power play shortly thereafter.
