The 24-year-old explosive right-hander has been included after Rilee Rossouw was ruled out with a foot injury, adding to the absences of former captain AB de Villiers (elbow), and fast bowlers Dale Steyn (shoulder) and Morne Morkel (back).
"De Bruyn is the latest player to be rewarded for consistently good form at franchise and South Africa A level," Cricket South Africa selection convener Linda Zondi said in a statement on Wednesday.
"He has an outstanding first-class career average of 48.73 and has made 423 runs at 60.42 in this season's four-day competition."
De Bruyn also offers an option as a part-time seam bowler.
On Monday, it was announced that Faf du Plessis, who recently led the side to series victories at home to New Zealand and away in Australia, would take over the test captaincy on a permanent basis as De Villiers battled to regain full fitness.
"Credit to AB de Villiers for the smooth way the leadership transition has taken place. Faf has done an outstanding job in the last two test series and our leadership is in very good hands," Zondi added.
Next Monday, Du Plessis will appeal his conviction for ball tampering during the series in Australia that resulted in him losing his entire match fee for the second test in Hobart.
The appeal represents an element of risk as he is flirting with the higher sentence of a one-match ban, which would rule him out of the first test in Port Elizabeth, should he fail.
Replacement wicketkeeper Dane Vilas and left-arm spinner Tabraiz Shamsi have been dropped from the squad that toured Australia last month.
The second test will be played in Cape Town from Jan. 2 and will be concluded in Johannesburg from Jan. 12.
Squad: Faf du Plessis (captain), Kyle Abbott, Hashim Amla, Temba Bavuma, Stephen Cook, Theunis de Bruyn, Quinton de Kock, JP Duminy, Dean Elgar, Keshav Maharaj, Wayne Parnell, Vernon Philander, Kagiso Rabada.
(Reporting by Nick Said; Editing by John O'Brien)
