Opting to bat after winning the toss, South Africa rode on Amla and Faf du Plessis' 109 off as many balls, setting the title contenders up for a massive total with their 247-run second-wicket partnership at the Manuka Oval here.
But the real carnage was unleashed in the slog overs as the Proteas smashed 110 runs in 8.3 overs with the fifth-wicket pair of David Miller and Rilee Rossouw going hammer and tongs.
During their belligerent unbroken partnership, Rossouw found the fence six times and cleared it thrice in his 30-ball 61, while Miller hit four boundaries and two sixes in his 23-ball 46.
Skipper A B de Villiers, who had smashed the world record for the fastest 150 in their previous game against the West Indies, missed out but still made 24 off just nine balls with two sixes and a four. Against the Caribbean nation last week, South Africa had amassed 408 for five.
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Spinner Andy McBrine, who was called for this match, was the most successful bowler for Ireland, returning figures of two for 63.
Amla hit 16 fours and four sixes, while du Plessis struck 10 boundaries and a six.
The South Africans scored 230 in the last 20 overs, leaving the Irish bowlers bruised and battered.
The Proteas not only found the fence with consummate ease but also ran the singles and twos regularly, adding to Ireland's misery.
South Africa have won all three of the previous ODIs against Ireland, two of which have come at World Cups -- 2007 and 2011.