An incredible unbeaten 138 from Quinton de Kock was not enough for South Africa as rain in Bloemfontein handed England a 39-run win on the Duckworth-Lewis method in the first one-day international.
A 73-ball century from Jos Buttler (105) - his slowest in the 50-over game - inspired England to 399-9, their highest overseas ODI total and the largest in any ODI at the Mangaung Oval.
Alex Hales, Joe Root and Ben Stokes all contributed with fifties, but the massive target appeared well in reach for the Proteas thanks to the brilliance of De Kock.
De Kock smashed 12 fours and six maximums in a stunning innings in which he appeared to struggle with a hamstring issue.
But South Africa were thwarted by the elements as a storm forced the players off the field on 250-5, comfortably adrift of the par score of 290 needed after 34 overs.
Openers Jason Roy (48) and Hales put on 68 for the first wicket as England made progress that was slowed somewhat following the former's departure, although Hales reached his half-century prior to exiting for 57.
But Buttler's arrival at the crease ratcheted the run rate back up as he pushed the pace with a devastating display of hitting, producing a fine stand of 97 with the patient Root.
Root eventually went for 52 courtesy of Chris Morris' (3-74) full delivery and captain Eoin Morgan (23) lasted only 21 balls, yet Buttler and Stokes (57) restored England's control with a partnership of 61 before the wicketkeeper's innings - which featured 11 boundaries and five maximums - was brought to a close.
Buttler picked out AB de Villiers in the covers, but South Africa were unable to stem the tide of England runs, Stokes and Moeen Ali (19) pushing the rate beyond 12 with 54 runs in a 25-ball stand.
A flurry of late wickets helped prevent England from reaching 400, but the tourists' attack struck early as David Willey (1-30) dismissed Hashim Amla for just six.
England's momentum soon vanished, De Kock and Faf du Plessis (55) matching the furious pace set by the tourists to hastily push South Africa into three figures.
However, De Kock found little in the way of support following Du Plessis' removal at the hands of Ali (3-43).
Indeed, De Villiers went for eight courtesy of a stunning one-handed running catch from Stokes and, while the ailing De Kock continued to do the heavy lifting, JP Duminy (13) and Rilee Rossouw (19) failed to get going, with the rain then arriving to rob the crowd of a potentially gripping finish.