Nokwe, a former township child who emerged from the development ranks to be one of the country's top wingers, will finally make his debut after touring with the Springboks in 2004 and coming close in 2006.
The lanky 26-year-old, who now plays for Currie Cup champions Free State, represented a South African XV against a World XV in Leicester two years ago but still has not touched the ball in a Test.
De Villiers believes Nokwe has earned his opportunity to show what he can do on the biggest stage.
"His selection is just reward because he showed his form in the Super 14 and Currie Cup," said De Villiers.
"I would never bring a player in if I did not think he would be an asset. I trust Jongi and back him and I believe he will step up to the occasion."
Considered by some to be as fast as the man he replaces - IRB Player of the Year Bryan Habana - Nokwe will want to show off his pace in front of Nelson Mandela, with the match in honour of the former president's 90th birthday celebrations.
De Villiers explained at the team announcement that both Habana and Schalk Burger could have played in the Johannesburg encounter but, with three tough Tri-Nations matches ahead, have been rested as a precaution.
"It's precautionary, we're blessed to be able to give them another week of recovery, but both could have played if we needed them," De Villiers said.
"We will see what happens on the field in terms of when we can use them off the bench, but we know they are ready."
The coach is overjoyed to have Fourie du Preez back, especially given his form with the boot in the World Cup.
"A kicking game was their flavour of the month in the World Cup and we do have Fourie du Preez back, so that is a huge asset for our kicking game," De Villiers said.