Aiden Markram will make his debut for South Africa in the first Test against Bangladesh to be played at Senwes Park, Potchefstroom, from September 28 to October 2.
The 22-year-old Titans opening batsman was a member of the Test squad during the England tour without playing a match and has also captained the South Africa A four-day squad.
The other uncapped player in the squad is all-rounder Andile Phehlukwayo. Phehlukwayo was also part of the tour group to England.
An extra all-rounder, Wayne Parnell, has been recalled to the 13-man squad with Vernon Philander, Chris Morris and Dale Steyn all ruled out through injury.
Wiaan Mulder has been invited to join the squad as cover for Parnell who will have to undergo a fitness test next week.
In the event of Parnell coming through successfully Mulder will be returned to the bizhub Highveld Lions for their Sunfoil Series match starting next Thursday.
The Test squad has been named for the first match only of the two-match series.
National selection convener, Linda Zondi, said: “Aiden has been knocking on the door for some time now.
“He gained valuable insight into the Proteas team culture during the tour of England and he has shown maturity beyond his years, having captained South Africa to victory in the under-19 World Cup and as captain of the South Africa A four-day side.
“The inclusion of Andile and Wayne provides the necessary all-rounders to give options as concerns the balance of the starting XI.
“The selection of some younger players is part of the process to build for the future and at the same time maintain our hard core of experience.”
Proteas Test squad: Faf du Plessis (capt), Hashim Amla, Temba Bavuma, Theunis de Bruyn, Quinton de Kock, Dean Elgar, Keshav Maharaj, Aiden Markram, Morne Morkel, Duanne Olivier, Wayne Parnell, Andile Phehlukwayo, Kagiso Rabada