Having not played a competitive match since March, the Proteas returned to international cricket in losing fashion against England at Newlands on Friday.
England skipper Eoin Morgan won the toss and elected to bowl in the first of three T20 internationals between the two sides.
The Proteas posted 179/6 in their allotted 20 overs, with Faf du Plessis top-scoring with 58 off 40 balls.
Rassie van der Dussen chipped in with 37 (28 balls), while skipper Quinton de Kock contributed 30 off 23 balls.
In their turn at the crease, England started slowly, but showed experience and patience in timing their innings to perfection.
The man of the match and hero for England was Jonny Bairstow who held his nerve to score an undefeated 86 off 48 balls to guide the visitors to 183/5, giving them victory by five wickets.
The sides will do battle in the second T20 at Boland Park in Paarl on Sunday. The first ball is due to be bowled at 14:30.
The third and final clash will take place back at Newlands on Tuesday, December 1 at 18:00.
Following the T20 series, the sides will do battle in three ODIs.
England are the reigning ODI Cricket World Cup champions.
Quinton de Kock (captain, wkt), Temba Bavuma, Faf du Plessis, Rassie van der Dussen, Heinrich Klaasen, Pite van Biljon, George Linde, Beuran Hendricks, Kagiso Rabada, Lungi Ngidi, Tabraiz Shamsi
Jason Roy, Jos Buttler (wkt), Dawid Malan, Jonny Bairstow, Ben Stokes, Eoin Morgan (captain), Sam Curran, Tom Curran, Chris Jordan, Jofra Archer, Adil Rashid
REMAINING PROTEAS V ENGLAND T20 AND ODI FIXTURES:
Sunday, November 29: 2nd T20I South Africa v England, Boland Park, Paarl – 14:30
Tuesday, December 1: 3rd T20I South Africa v England, Newlands – 18:00
Friday, December 4: 1st ODI South Africa v England, Newlands – 13:00
Sunday, December 6: 2nd ODI South Africa v England, Boland Park, Paarl – 10:00
Wednesday, December 9: 3rd ODI South Africa v England, Newlands – 13:00