Mulder, 20, was added to the 13-man squad which hammered Pakistan in all three Tests in a home series earlier this season.
"Wiaan has been part of our strategic thinking in developing a batting all-rounder for the Test squad for some time," said selection convener Linda Zondi in announcing the squad on Thursday.
Mulder was part of the Test squad for a series against Australia last season couldn't make it to the playing XI. He picked up an ankle injury during a one-day international against Zimbabwe last September but made a successful comeback to first-class cricket for the Lions franchise last month.
Another notable omission from the squad is paceman Lungi Ngidi, who is recovering from a knee injury sustained during a limited overs tour of Australia in November.
Ngidi has been training with the South African limited overs squads in recent weeks but Zondi said the selectors were handling him with caution.
"We are not going to rush him back into international action until he has had the time to regain full match fitness," said Zondi.
Sri Lanka are likely to face an uphill task with an inexperienced team, which includes only six of the players defeated in all three Tests in South Africa two seasons ago. Their squad includes nine players who will be touring South Africa for their first time.
Faf du Plessis (captain), Hashim Amla, Temba Bavuma, Theunis de Bruyn, Quinton de Kock (wkt), Dean Elgar, Zubayr Hamza, Keshav Maharaj, Aiden Markram, Wiaan Mulder, Duanne Olivier, Vernon Philander, Kagiso Rabada, Dale Steyn