Close on 10,000 of the tickets were snapped up just after Wales confirmed that the game would kick off at 2.30pm on the summer Saturday afternoon.
Family discount sales have also proved a big attraction with groups hoping to enjoy a day in the sun for Welsh rugby.
The early boost in sales has been achieved in the hours after the tickets went on sale to the public at 9am on Monday.
With just under eight weeks to go before the game the Welsh Rugby Union is now hoping for a bumper crowd to cheer on the team.
WRU Group Chief Executive, Roger Lewis, said: "I am delighted with the fantastic interest the game has already generated.
"We are never complacent about ticket sales but these figures give us great confidence that we can look forward to a great occasion.
"The game will also be an opportunity for Welsh fans to give the squad a great send-off for their June tour of New Zealand where they play the All Blacks twice.
"South Africa play every match to win but I know that Warren, his coaches and the squad are determined to give their all."
The Wales v South Africa fixture is also being seen as the start of the serious build-up towards the 2011 Rugby World Cup.
Over two thousand tickets were sold in the first few hours of public sale to add to the 25,000 plus tickets snapped up by clubs, debenture holders and WRU ezine subscribers during pre-sale.
As interest in the clash against the Springboks continues at a steady pace, Wales will be hoping for a full house in Cardiff before they travel to New Zealand on tour this summer ahead of the 2011 Rugby World Cup.
Tickets can be purchased from £25 per person or £80 for a family ( 2 adults, 2 children) at the WRU's Cardiff Arms Store (No 8 Westgate Street, Cardiff); via Ticketmaster (tel 08442 777888, www.ticketmaster.co.uk), Ticketline (02920 230130, www.ticketlineuk.com) and via www.wru.co.uk/tickets.
WRU hospitality prices start at £99 for the 'Bar 10 Braai' package which celebrates the South African barbecue custom known as braai. Fans should act fast to secure the hottest tickets via the official website www.millenniumstadium.com
Further hospitality information is available online for all packages including the 'Platinum Suite' at £229 and the 'SA Gold' at £119 plus vat per person.