The veteran centre-back, who earned 29 caps for Bafana Bafana, has been plagued by injury, and has called time on his career on medical advice.
Sangweni was restricted to six league starts for the Buccaneers this season, having previously been a key performer for the Soweto giants following his signing from Golden Arrows at the start of 2011/12.
The 34-year-old’s last match for Pirates was on November 29, 2015 against Etoile du Sahel in the CAF Confederation Cup final in Tunisia.
“Today, I’ve asked this press conference because I want to announce the premature retirement of Siyabonga Sangweni,” said Khoza.
Siyabonga has been plagued by injury and after consultation, the medics have confirmed that he has to end his career early.
“Siyabonga Sangweni has been a stalwart for this club and has been a great leader. He has shown great commitment.
“I wish him success with all his future endeavours. I thank him for his leadership qualities.”
He added: “We spoke to the team this morning, so it has been an emotional time to say goodbye to a great player like him.”
Meanwhile, Khoza revealed Bucs assistant coach Tebogo Moloi has been granted leave for personal reasons, while he indicated Senzo Meyiwa’s family’s issues regarding an insurance payout could be resolved by next week.