South Africa bundled West Indies out for 204 secured a bonus point and topped the table. The result meant the St Kitts' segment of the series ended with all three teams in the same position as they were after the Guyana leg.
Australia, South Africa and West Indies have played four matches, won two and lost two. In the lead up to Wednesday, Amla stressed the need for the top six to take more responsibility.
On Wednesday, he stood by those words and shared in a 182-run opening partnership with Quinton de Kock.
Allrounder Chris Morris. who returned from a hamstring niggle, was promoted to No. 3 and provided a quick cameo before Faf du plessis led the late assault. South Africa plundered 105 runs off the last 10 overs.
Although this was the best surface for batsmen in the series so far, West Indies' bowlers lacked control and penetration.
Four of their six-man attack conceded more than six runs an over with only the spinners, Sunil Narine and Sulieman Benn, able to hold up an end. The pacemen could not find the right lengths and runs came easily for South Africa.