The tourists, who had needed only a draw in Johannesburg to pull off an improbable 1-0 success, were instead beaten just before lunch on the fourth day.
Morne Morkel (4-59) was the man who at last ensured South Africa landed the 'knockout blow' their captain Graeme Smith had craved, taking 3-0 in seven balls to put paid to England's apparent decision to pin all hopes of survival on an ambitious counter-attack.
Paul Collingwood (71), England's top runscorer of the series, provided the impetus behind an unlikely and short-lived bid for glory. His half-century included 10 fours from only 65 balls.
Support, however, was in short supply.
Twice England had clung on for draws in this epic series. But after starting a cloudy morning 195 behind with only seven second-innings wickets left, it was clear this time Collingwood was going to try to wrest the momentum back.
He took on the short ball from Morkel and Dale Steyn with a series of upper-cuts and hooks.
His adventure was a startling contrast with the near strokeless policy which saw him bat 66 overs for 40 to salvage the third Test in Cape Town.
In the final Test, he reached the same number of runs from only 44 balls, compared to the 188 he ate up at Newlands.
Kevin Pietersen, though, did not score a run until the fifth full over of the day and Collingwood had made 32 to his partner's three in the session when Pietersen chased an attempted wide drive on the up off Wayne Parnell and edged behind.
Collingwood survived a decision review system appeal for lbw from the first ball of Morkel's second spell and another close call when Parnell swung one into his pads too. But Ian Bell fell to a fine delivery from Morkel, edging high to second slip.
Then Matt Prior made a second-ball duck, mis-hooking a lobbed catch to Smith, having survived a half-chance to short-leg from his first delivery.
A DRS review proved Stuart Broad had, in fact, gloved Morkel behind down the leg-side after initially being given not out by Steve Davis.
Graeme Swann survived once in a typically breezy 20, Ashwell Prince unable to complete a diving catch in the gully off Morkel, before Steyn instead had him edging into the slips.
But despite Collingwood's defiance which included hitting Steyn for six over long-off, the end was nigh. When Collingwood pulled the first ball of JP Duminy's one-over spell to be caught at deep square-leg, it was an anti-climactic conclusion for the Durham all rounder.
The series finished similarly when Duminy took the last wicket, Ryan Sidebottom bowled slog-sweeping as England folded in fewer than 43 overs.