Lara Goodall hit eight boundaries in her unbeaten 93 in Dublin on Tuesday
South Africa strolled to a nine-wicket victory and 2-0 series lead against Ireland in the three-match ODI series at Clontarf.
Ireland were skittled out for 69 in the opener but made 213-8 on Tuesday with skipper Gaby Lewis hitting 59.
Georgina Dempsey added 45 late-order runs but the total was easily surpassed by the tourists in just 38.4 overs.
Lara Goodall scored 93 and her unbeaten 165-run partnership with Andrie Steyn (84) ensured a comfortable win.
Ireland also lost by nine wickets on Saturday but this was a much improved batting display with Lewis again leading from the front.
She lost opening partner Leah Paul with just two runs on the board and Ireland were 135-5 before Lewis and Sophie McMahon (42) put on a 69-run stand.
Dempsey was unbeaten after an impressive knock while Shabnim Ismail was the pick of the South African bowlers with 3-31.
Laura Wolvaardt was dismissed by Dempsey for 27 to leave the Proteas on 52-1 but that was as good as it got for the hosts as Goodall, who was dropped on 10, and opener Steyn took charge.
Goodall's 93 came at nearly a run a ball as the pair combined for South Africa's sixth highest partnership in ODIs.
South Africa won the T20 series 2-1 and they will be looking to finish their tour with another victory when the sides meet again at the Dublin venue on Friday.
