They replaced allrounder James Hopes and bowler Brett Dorey, who were Tuesday part of the victorious Australian team to win the triangular series against Sri Lanka and South Africa.
The omission of pace bowler Glenn McGrath had been expected after he ruled himself out of the first part of the South African tour while he remains in Australia with his wife as she undergoes treatment for cancer.
Watson is returning to the side after surgery for a shoulder injury sustained during a match against the West Indies in November while Johnson has been given another chance to impress after playing in the Chappell-Hadlee Series in New Zealand in December.
Opening bat Phil Jaques has again missed out on selection despite belting 94 runs on his debut, and only appearance, for the Australian one-day team.
"We have picked what we consider a well-balanced squad. There is a good blend of youth and experience in the team for what promises to be a challenging series," chairman of the national selection panel Trevor Hohns said.
Australia will first play a Twenty20 match in Johannesburg on February 24 followed by five one-day internationals beginning February 26.
Australia - Ricky Ponting (captain), Adam Gilchrist, Nathan Bracken, Michael Clarke, Stuart Clark, Brad Hogg, Michael Hussey, Mitchell Johnson, Simon Katich, Brett Lee, Mick Lewis, Damien Martyn, Shane Watson, Andrew Symonds.