The visitors first dismissed India cheaply for just 114 runs and then relied on Tryon's knock to overhaul the target with 8.5 overs to spare.
Tryon, whose previous highest ODI score was an unbeaten 15, was star of the day with a 50-run knock as she showed patience to bat with lower-order batters.
Walking into the middle at 68 for six after the dismissal of Van Niekerk, Tryon reached her half century in 78 balls and was run out immediately after that.
The three-match ODI series is a part of the seven-round ICC Women's Championship, which is a qualifying tournament for the 2017 ICC Women's World Cup.
The Indians had come into the match with loads of confidence following their win in the one-off Test against the visitors but were done in by fast bowler Marizanne Kapp and leg-break bowler Dane Van Niekerk.
The Indian batters could never recover from early jolts even as Harmanpreet Kaur and Jhulan Goswami tried their best to give a respectable run-chase for the visitors.
Apart from them, the batters who managed to reach the double digits were V R Vanita (11), Smriti Mandhana (11) and Poonam Yadav (13 not out).
Kapp and Niekerk devastated the Indian batting lineup as they regularly claimed wickets, hardly giving any chance for the hosts to make a comeback.
In 29.2 overs, half of the Indian batters had returned to the pavilion with a score of 93 on the board and in next 57 balls the hosts innings folded after adding just 21 runs.
The South African chase also was no different from the Indians, as half of their team was out with just 31 runs on the board, with Jhulan and Harmanpreet doing the damage.
Jhulan was star wicket-taker for India with figures of three for 22, and both Shubhlakshmi Sharma and Harmanpreet bagged two wickets each.
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