Quinton de Kock led South Africa to an 18-run win over the USA, helping his team to a mighty total of 194/4 as they batted first in the Super Eights.
In their response, USA reached 176/6 thanks to a superlative innings from Andries Gous, 80 not out from 47 balls.
The USA were the story of the opening round, stunning the cricket world to progress from Group A along with India at the expense of Pakistan, Canada and Ireland.
The co-hosts produced the shock of the tournament when they beat Pakistan in New York, and will be looking to take another major scalp at the Sir Vivian Richards Stadium in Antigua.
South Africa won all four of their fixtures in Group D to progress to the Super Eight stage, but were pushed close in a number of those matches and will be looking for a confidence-building statement against the lowest-ranked team in this stage of the tournament.
Reeza Hendricks stayed only until the end of the third over, edging Saurabh Netravalkar straight into the air and ending up in the hands of Corey Anderson at mid-off.
So it was left to De Kock to push on with the assistance of Aiden Markram, hitting a brilliant 74 off 40 balls - including seven fours and five sixes. He was eventually removed by a smartly-delivered full toss from Harmeet Singh, caught by Shayan Jahangir.
And Harmeet struck again with the next ball, catching new batter David Miller off his own bowling, and making the scoreline 126/3 with a little more than seven overs remaining.
Markram was next to fall after a solid 46 off 32 balls, caught by a flying Ali Khan off Netravalkar.
Then Tristan Stubbs and Heinrich Klaasen formed an effective partnership for the last five overs, putting on a valuable 53 between them.
Gous was the stalwart for the USA as they endeavoured to make in-roads into the target of 195.
He lost his fellow opener Steven Taylor in the fourth over of the innings, caught by Klaasen off Kagiso Rabada for 24.
And Aaron Jones followed for a disappointing duck off five balls, caught by De Kock off the bowling of Keshav Maharaj after an edge behind, leaving USA on 56/3 after seven overs.
Corey Anderson went for a run a ball 12, bowled by Anrich Nortje's delightful full delivery, and Shayan Jahangir was dismissed for 3 off the first ball of Tabraiz Shamsi's spell.
It was Harmeet Singh who joined Gous at the crease in the 12th over, with USA on 76/5. Between them, they gave the rowdy fans at North Sound something to cheer - and with Shamsi's final over going for 22, including three sixes, they must have had hope of a famous win.
However, with Rabada's first delivery of the penultimate over luring Harmeet only into the hands of Stubbs and ending an innings of 38 off 22 balls, the dreams were ended.