Tendulkar brought down the curtain on a record-breaking 24-year career against West Indies last month amid an nation-wide outpouring of goodwill.
The 40-year-old 'Little Master' leaves behind a giant-sized gap to fill - 34,357 international runs to be precise - but Dhoni believes India have "moved on" as they prepare to face the top-ranked Proteas.
Rising star Virat Kohli is likely to take over Tendulkar's position at four while in the likes of Murali Vijay, Shikhar Dhawan, Cheteshwar Pujara and Rohit Sharma, not to mention Dhoni himself, ensure the tourists still boast one of the strongest batting line-ups in the world.
"With the last Test match we played in India, it is 100 percent sure that Sachin won't be available for any more international series," Dhoni told a press conference.
"It was always good to have him, but now that he won't be there, we have to concentrate on what he have in our hands.
"We have accepted that fact and moved on."
While India boast an exciting crop of young players they have little experience of playing away from their home conditions on the sub-continent in the five-day game.
Sharma, Dhawan and potential number six, Ajinkya Rahane, are yet to play on foreign soil while Pujara and Vijay have not made an away appearance in over two years between them.
In fact India have not played an away Test since being whitewashed 4-0 in Australia two years ago.
"Every series is a fresh start," Dhoni said.
"There is no point bringing excess baggage. It is about getting used to conditions and offering what the team has.
"There are plenty of youngsters in this side, who will get exposure by playing competitive cricket at the Test level. So it's a big positive for us."
South Africa skipper Graeme Smith wants his side to "hit the ground running" after they lost the opening Test of their recent drawn series against Pakistan.
The Proteas had little cricket before they travelled to the United Arab Emirates for that series, but now in the midst of their domestic summer he has warned their is no excuse for being caught on the hop.
"Most of the guys have played more cricket now, which is always good," he said.
"We have discussed the areas where we let ourselves down in that first Test against Pakistan.
"We responded well and we have played some positive cricket since then. We understand that tomorrow and this first Test is an important Test match in a two-match series; we can't afford to take a day or two to hit our straps."
Smith named his starting XI on Tuesday with Hashim Amla returning in place of Dean Elgar after he missed the second Test of the Pakistan series on paternity leave.
Amla adds strength to the Proteas batting and Smith thinks that is where the first Test will be won and lost.
"Batting in South Africa is probably one of the toughest places to bat against the new ball," he said.
"If we can set up good platforms and give ourselves the opportunity to post totals, then I think we will give ourselves a good chance of winning the Test match."