India have won just three times in 16 one-day internationals against the host nation in South Africa and suffered a 37-run defeat in their only warm-up match against a Rest of South Africa team in Benoni Thursday.
Only captain Rahul Dravid of the Indian top order was able to handle the pace of Dale Steyn in Benoni and it will be a relief to the Indians that South Africa's fastest bowler is not in the national one-day team.
Even so, the tourists can expect some aggressive pace bowling from Makhaya Ntini, Shaun Pollock, Andre Nel and Jacques Kallis as South Africa seek to take advantage of the bounce and pace usually on offer from on home pitches.
Both Dravid and coach Greg Chappell said they expected an improvement on Thursday's performance, pointing out that the Indians had barely had time to adapt to South Africa conditions before playing in Benoni.
Chappell said Dravid, who made 79, had provided an object lesson to younger players in the side on the art of playing pace bowling in difficult conditions.
For both teams, the series is part of the build-up to the 2007 World Cup in the West Indies.
South Africa named the same 14-man squad that reached the semi-finals of the recent ICC Champions Trophy in India - where India failed to reach the knockout stage - for the first one-day international.
"We want to build up a winning momentum," said South African coach Mickey Arthur, who said it was unlikely major changes would be made before the World Cup. "We have decided on the bulk of the squad," said Arthur.
"There is a bit of a debate about one or two places but we want players to gain confidence in the roles we expect them to play."
It is the first one-day international to be played at the Wanderers since the world record "438" game last season when South Africa overhauled a huge Australian total of 434 in a riot of run scoring.
The Indians have experienced being on the wrong side of a high-scoring match at the stadium. Sachin Tendulkar and Sourav Ganguly both scored centuries as India made 279 for five five years ago - only for South Africa to sweep to victory by six wickets with a hundred by Gary Kirsten.
Tendulkar is the only one of the three century-makers in action this time and as always the world one-day run-scoring record-holder will be a key player.
Whether or not Tendulkar will have the quick-scoring Virender Sehwag as his opening partner is uncertain after Sehwag missed the Benoni warm-up. He needed four stitches after suffering a cut to the ring finger of his right hand during fielding practice before the match.
India's bowlers can expect to come under pressure from a hard-hitting South African middle and lower batting order. Both Munaf Patel and Shanthakumaran Sreesanth took some heavy punishment in the closing overs in Benoni.
Likely to play important roles will be leg-spinner Anil Kumble and left-arm seamer Zaheer Khan, who both bowled impressively in Benoni after being recalled to the Indian one-day team.
India: Rahul Dravid (captain), Virender Sehwag, Sachin Tendulkar, Wasim Jaffer, Mohammad Kaif, Suresh Raina, Dinesh Mongia, Mahendra Singh Dhoni (wk), Irfan Pathan, Dinesh Karthik, Zaheer Khan, Anil Kumble, Shanthakumaran Sreesanth, Harbhajan Singh, Munaf Patel and Ajit Agarkar.
South Africa: Graeme Smith (captain), Jacques Kallis, Loots Bosman, Mark Boucher (wk), AB de Villiers, Boeta Dippenaar, Herschelle Gibbs, Andrew Hall, Justin Kemp, Charl Langeveldt, Andre Nel, Makhaya Ntini, Shaun Pollock and Robin Peterson.
Umpires: Billy Doctrove (WI), Brian Jerling (RSA). TV umpire: Ian Howell (RSA)
Match referee: Chris Broad (Eng)