Opener De Kock smashed 74 runs from just 40 balls and captain Aiden Markram added 46 for the Proteas as their top order finally fired after enduring a difficult start to the tournament.
Even though Harmeet Singh (2-24) removed De Kock and David Miller (0) in consecutive balls in the 13th over, Heinrich Klaasen (36 not out) and Tristan Stubbs (20no) helped South Africa to a healthy 194-4 in Antigua.
USA fell to 76-5 just after the midway point of their innings as it looked like a chase of 195 would fall flat, but a magnificent partnership of 91 from 43 balls between Andries Gous and Harmeet took USA to within 28 of their target with two overs to spare.
However, Rabada took the crucial wicket of Harmeet for 38 and killed the contest as his 19th over went for that wicket and just two runs, capping a fine bowling display that saw him finish with figures of 3-18 from four overs.
Gous batted on and finished with an impressive unbeaten 80 off 47 balls, but USA fell short as South Africa maintained their 100 per cent record in the competition so far.
Data Debrief: De Kock and Gous impress
After USA won the toss and elected to field before removing Reeza Hendricks (11) in the third over, they sensed an opportunity to seize control.
But De Kock had other ideas, smashing three successive sixes as South Africa scored a huge 28 off the fourth over to seize momentum they did not relinquish from there.
De Kock’s superb innings included five maximums and seven fours until he was finally removed by Harmeet in the 13th over.
As the South Africa star left the field, only three players had recorded a better innings than him in this year's tournament – West Indies' Nicholas Pooran (98), USA's Aaron Jones (94 not out) and Afghanistan batter Rahmanullah Gurbaz (who has had scores of 80 and 76).
But Gous then immediately topped him with an excellent knock of his own, and the American now has the most runs in the tournament with 182, putting him 15 ahead Gurbaz, who is back in action against India on Thursday.
Defending 121, the Strikers' left-arm spinner picked up a hat-trick in the first over of the innings, dismissing Andries Gous, Dewald Brevis and Ibrahim Zadran, to leave Samp Army reeling at 1 for 3.
In his second over, he removed the opposition captain Faf du Plessis and Najibullah Zadran in space of three balls to further rattle Samp Army.
Jason Holder's 22 of 11 and Qais Ahmad's unbeaten 31 off 13 at No.10 meant Samp Army huffed and puffed to 80 for 9.
Earlier, opener Rahmanullah Gurbaz's blazing 56 off 28 set the tone for Strikers to post a competitive 121 for 5. His knock included four fours and five sixes.
In the end, Asif Ali smashed three fours in his unbeaten seven-ball knock of 17 to further lift Strikers.
Samp Army will have a second chance to make the final when they play the winner of the Eliminator between Bangla Tigers and Deccan Gladiators in Qualifier 2 later today.
At the time of publishing, the Tigers were 78-4 off seven overs batting first.
In their T20 World Cup debut, the US have two wins from two and top Group A after beating Canada in their opener before following it up with another statement victory.
The US opted to let Pakistan bat first, limiting them to 159-7, and chased down the target exceptionally well, with Nitish Kumar hitting a four on the final ball to force a super over.
Pakistan still had no answers, falling to a five-run defeat in their opening game at the tournament.
Patel did not play in their opening game against Canada but came in to get 50 off 38 balls, including two fours and two boundaries, but quickly shifted the focus to the whole team.
"Playing in the World Cup, you don't get a chance to do it every year," he said. "We knew we had to be fully committed [to] every single ball against Pakistan. It was a complete effort from the team.
"It's a big achievement - beating Pakistan while playing for the first time. Complete performance. We used the conditions well. Kept them to 160, which was chaseable. Happy with my contribution, happier to have won.
"Plan was to have a big partnership among top three and then to take it deep. [Andries] Gous played cricketing shots and took pressure away. As a player and captain, you want to show off your talent on the big occasion. Wanted to score in a winning cause."
Pakistan struggled to get going, with captain Babar Azam finishing on 44 after a slow start to the game saw them struggle to build any momentum.
Despite eventually finishing the first innings strongly, Pakistan struggled to limit the US' chase, with errors creeping into their game to keep the tournament co-hosts in with a chance.
Azam highlighted their slow starts to both innings as their shortcomings in the loss.
"First six overs while batting, we couldn't capitalise. We took momentum but back-to-back wickets hurt us," he said.
"We were not up to the mark in the first six [while bowling]. Didn't take wickets, spinners didn't either. We came back in the end but couldn't finish well. Hope to do well in the future.
"[Result makes it] very hard. All credit to USA who did well in all three departments. That's why they won. There was moisture in the pitch. It was two-paced. As professionals, we had to assess conditions better."
Suryakumar Yadav hit an unbeaten half-century as India successfully chased down their opponents' target of 111 for a seven-wicket victory - and their third win in as many Group A matches.
The tournament co-hosts also entered the contest with a perfect record from their opening two games, but endured a poor start as Arshdeep Singh claimed Shayan Jahangir and Andries Gous in the first over.
That left them at 3-2, but they managed to settle with Steven Taylor (24 from 30 balls) and Nitish Kumar (27 off 23) top-scoring as their side finished at 110-8.
However, the States made a purposeful start in the field. With the second ball, Virat Kohli was gone for a duck as Gous caught him from Saurabh Netravalkar, who also dismissed Rohit Sharma for just three.
Suryakumar (50 off 49 not out) stepped in and held the fort alongside Shivam Dube (31 off 45 not out), though India were still in danger of a potential shock, needing 35 off the final 30 balls.
Nevertheless, an untimely five-run penalty was awarded to them as the USA took longer than a minute between overs for the third time.
That swung the pendulum firmly in India's favour. Successive boundaries from Suryakumar eased the pressure as they saw out what was eventually a comfortable win.
Data Debrief: India through, but Kohli's struggles continue
It was not as comfortable as India would have hoped for but, nevertheless, they managed to get the job done, with Suryakumar leading the charge.
However, the form of Kohli will be a cause for concern. His dismissal for a golden duck means he has now scored just five runs in his nation's opening three matches.
