Averaging 54.23 in One-Day internationals, the wicketkeeper batsman has a strike-rate of 100.23 with 24 100s and a high score of 162 not out.
But Duminy (28 not out) and South Africa captain AB de Villiers (27 not out) completed a win in a match where only 60 overs out of a scheduled 100 were bowled.
Fast bowlers Kagiso Rabada and Wayne Parnell snared seven wickets as South Africa bowled England out for just 153 runs after a top-order collapse in their third and final one-day worldwide on Monday.
The hosts collapsed to 20 for six - the first time any side had lost six wickets in the first five overs of a one-day worldwide - after being sent into bat in overcast conditions and on a green-tinged pitch at "the home of cricket". While Jonny Bairstow engineered a partial recovery, he could not prevent England slipping to their first defeat in nine ODIs.
Toby Roland-Jones showed no fear on his debut, hooking Chris Morris into the Grandstand for six and then driving Parnell beautifully through the covers a few balls before a sweep to the fence took Bairstow to his half century, off 63 balls.
Keshav Maharaj was the man who missed out on Stokes early wicket but eventually bagged him for 101 when he holed out to David Miller in the deep.
Left-arm spinner Maharaj took three for 25 in 6.1 overs.
Chris Morris joined the battle with the Proteas needing 69 off 39 balls and his 36 off 22 almost helped them home along with Miller's 71 not out but the pair got the jitters in the final over and couldn't get Wood away allowing England to wrap a 2 run win to claim a 2-0 series win.
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An overcast morning and a green-tinged pitch meant it was no surprise when de Villiers opted to field first upon winning the toss.
As it turned out, the Proteas only needed a mere five overs to have England six down.
Jason Roy fell in the first over and Joe Root quickly followed six balls later, the latter trapped lbw by Wayne Parnell for just two runs. "We have two hard matches straight up against Australia and England and if we don't start well the tournament's over".
Eoin Morgan, the England captain was caught behind off Parnell at the end of the fourth over.
The Middlesex man, who was left high and dry at the end as Maharaj snuffed out Jake Ball and Finn with minimal fuss, will look more fondly on his maiden worldwide wicket as Amla chopped on to his stumps after the post-interval resumption. It was the start of a brilliant over that yielded three wickets in five balls for Rabada. Jake Ball found some swing as Lords clouded over and quickly dismissed de Kock and Faf du Plessis.
Successive poor shots, with Jos Buttler and Adil Rashid falling to consecutive deliveries by playing nearly identical shots, left the hosts facing an uphill battle by the fifth over.
Only New Zealand, who made 359-3 in 2013, have scored more in an Ageas Bowl ODI than either side.
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