The clash is the first of the three-match Royal London Series between the countries, and will come hot on the heels of the Test match between the sides at Taunton.
The final two matches of the ODI series take place in Bristol and Leicester, before the sides meet in three T20 internationals in Chelmsford, Worcester and Derby.
The match at the County Ground will also be shown live on Sky Sports.
England Women last played in Northampton in July last year when they won a rain-affected T20 international against India.
Natalie Sciver hit top-scored with 55 as England posted 177 for seven in their 20 overs, before rain ended India's reply on 54 for three to secure an England win by 18 runs.
As well as the series against South Africa, England's women will also be competing in the Commonwealth Games in Birmingham and then taking on India in a white ball series in September.
They defend their ICC Women's World cup crown in New Zealand next month.
Managing director of England women’s cricket, Clare Connor, said: “We are thrilled to be able to announce a compelling summer of international women’s cricket against two of the best teams in the world, in what is a bumper year for the women’s game.
“With the second edition of The Hundred and the historic opportunity to participate in the Commonwealth Games on home soil, we’re looking forward to seeing our players thrive on the biggest stages.
“Despite the challenges presented by the pandemic, we keep seeing growth in our female participation numbers and I’m optimistic that a summer as action-packed as this, with more days broadcast than ever before, will continue to inspire more women and girls to play and watch the game.”
Northants supporters can register their interest in securing tickets for the England versus South Africa clash online at https://nccc.co.uk/news/the-county-ground-to-host-england-women-odi/