The 34-year-old bows out as the most capped prop in South African history with 117 caps.
Nicknamed 'Beast', Mtawarira was a standout performer as the Boks beat England in last Saturday's World Cup final, winning a number of scrum penalties.
"I've been privileged to play this great game and achieve many career goals over the last 12 years of playing senior rugby," said Mtawarira.
"I've been blessed to have been part of teams that achieved so much success over the years, and I have many memories to cherish forever, but I can honestly say that winning the Rugby World Cup is the perfect ending and cherry on top.
"I am grateful for the opportunities afforded to me by many top coaches at the Springboks and the Sharks, and grateful to my numerous team-mates in green and gold, and black and white, over the years."
Mtawarira retires as the third-most capped Springbok behind Victor Matfield (127 caps) and Bryan Habana (124).
He won his first cap against Wales in 2008 and also has the most appearances of any South African in Super Rugby with 159, all for the Sharks.