Akila Dananjya spun a web and put the South Africans on the back foot as they were on 94 for 7 after 18 overs, chasing 300 to win at Khettarama.
Earlier, Angelo Mathews finished three runs short of a first ODI hundred in Sri Lanka and first against South Africa, but his run-a-ball 97 took Sri Lanka to an imposing total on a surface that is slowing down.
As a result, South Africa will need to pull off the highest successful chase at this venue and the hosts can be satisfied with their most complete batting performance in a full inning in this series.
Four fifty partnerships held together with an innings in which Sri Lanka showed aggression against an inconsistent but ever-threatening South African pack.
Keshav Maharaj was the stand-out performer and put in the most economical performance of his short ODI career.
Maharaj's 10 overs cost only 32 runs as he found turn and proved difficult to get away.
