A cameo of 39 from only 11 deliveries from Moeen Ali helped England to a formidable 204 for seven but it was put in the shade by De Kock, whose 17-ball fifty under the floodlights was the fastest by a South African in T20s.
The shell-shocked tourists were grateful when he was caught in the deep for 65 from 22 balls, which included two fours and eight sixes, but Rassie Van Der Dussen and Dwaine Pretorius almost carried South Africa to victory.
Tom Curran was left to defend 15 in the last over and though Pretorius bludgeoned a six then a four, he was trapped lbw for 25 and with three needed from the final ball, Bjorn Fortuin ramped a slower delivery to Adil Rashid at short fine-leg.
England therefore prevailed to make it 1-1 – having lost at East London in a match that also went to the wire – and set up a decider at Centurion on Sunday.
Having been asked to bat first they were grateful for Jonny Bairstow's 35 off 17 balls before Moeen thrashed three fours and four sixes, dominating a 51-run stand with Ben Stokes that spanned 17 legal deliveries and 14 minutes.
Stokes finished on 47 not out off 30 balls – remarkably his best return in Twenty20s for England – before taking the catch in the deep that saw off De Kock in a South Africa innings where Mark Wood, Chris Jordan and Curran finished with two wickets apiece.
After Jos Buttler's loose swing took a thin outside edge to give Lungi Ngidi the breakthrough at the start of an unchanged England's innings, Bairstow and Jason Roy peppered the boundary rope in a 52-run partnership.
Bairstow capitalised on Fortuin, included at the expense of Dale Steyn, dropping a sharp caught and bowled chance when the Yorkshireman was on one by unfurling a series of powerful drives.
Roy exquisitely clubbed the expensive Beuran Hendricks into the crowd beyond extra cover while Bairstow clattered back-to-back sixes off Andile Phehlukwayo before being bowled through the gate later in the over.
Roy (40) and Eoin Morgan (27) were both caught on the fence while Joe Denly made just one before deflecting on to his stumps, deceived by Phehlukwayo's leg-cutter in an ugly dismissal as England staggered from 90 for two to 125 for five.
However, that merely set the scene for Moeen, who at one stage threatened to shatter the fastest England T20 fifty, in a staggering cameo where seven of the balls he faced went for either four or six.
Hendricks was smashed over deep square-leg and long-on in the space of three balls while a remarkable slice off Ngidi flew over deep backward point. Moeen then sent a catch to long-on but the damage had been done.
After Stokes' towering six had carried England beyond 200 and the second highest T20 total at the ground, Moeen was on the receiving end of some punishment as De Kock carted the off-spinner for three sixes in four deliveries.
It was not just Moeen that De Kock manhandled as all of England's frontline attack went the distance at least once, punished for erring in line and length as De Kock etched his name into South Africa's history books.
He finally mistimed one as a Mark Wood full toss was caught at deep midwicket, with the wicket standing to De Kock's evident frustration despite a marginal call on height following multiple television replays.
Temba Bavuma was unable to take the reins as he departed for 31 after gloving a Wood bouncer down the leg-side while dangerman David Miller flickered in his 21 before being caught at long-on off Stokes.
Despite wickets in hand, the asking rate was starting to climb as 50 runs were required from the last four overs, a period in which England had earlier smashed 68.
Jordan bowled both JJ Smuts and Phehlukwayo with successive deliveries but Wood yielded 19 runs in the 18th over as Van Der Dussen (43 not out) hammered the paceman for two sixes.
However, England, and Curran in particular, were able to hold their nerve when it mattered most.