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.