The former SuperSport United, Mamelodi Sundowns and Al Ahli manager takes the South Africa reins for the second time after previously managing the team from 2010 to 2012.
Mosimane took over from Carlos Alberto Parreira after the 2010 World Cup but was unable to steer his side to the 2012 Africa Cup of Nations.
He also served as caretaker coach in 2007.
The announcement was made by the South African Football Association at a press conference held at SAFA's headquarters in Johannesburg on Tuesday morning.
Speaking after his appointment, a delighted Mosimane said: "I have been given the privilege of leading our national team again.
"I take this responsibility knowing that I still have something to give in football, especially in my country.
"I know this is simply not a coaching job; it is bigger than Pitso Mosimane.
"I understand the weight of this role, the expectations that come with it, and what this team means to South Africa. With pride and determination, I accept the challenge."
Mosimane's first task is to guide Bafana to the 2027 Africa Cup of Nations, where his side have been drawn in Group D alongside Guinea, Eritrea and Kenya - who have already qualified as one of the co-hosts.
