Chasing a mammoth target of 394, the South Africans were 160 all out after facing 35 overs with the top-score coming from Paul James, batting at number 7, with 41.
Daniel Bosman struck 4 while Corne Botha was unbeaten on 36 but it was a poor batting effort from the home side at Willowmoore Park.
Earlier, India opening pair of Vaibhav Sooryavanshi and Aaron George both hot centuries as the tourists posted 393-7 in their 50 overs.
Sooryavanshi was the more aggressive with 127 in just 74 balls that included 10 6s and nine 4s.
George was more circumspect but still impressive as his 118 came in 116 deliveries in an partnership of 227 at the top of the order.
Vedant Trivedi hit 34 while the innings received a late boost as Mohamed Enaan scored 28 not out off 19 balls.
Both teams used the series to fine-tune plans ahead of the ICC U19 World Cup that starts on 15 January and will be co-hosted by Zimbabwe and Namibia.
The South Africa U19s fell to a series defeat in the youth ODIs against their India counterparts after losing the second game by eight wicket (DLS) in a rain-affected encounter in Benoni.
South Africa's Jorich van Schalkwyk became the first batter in youth ODI history to score a double century as U19 began their tri-series with a thumping 278-run win over hosts Zimbabwe in Harare.
