The Tyamara family released a statement on Friday morning confirming that the musician – who was known for his popular hits including "Mphefumlo Wami" and "Ndixolele" – had passed away just after midnight at the Edenvale Hospital.
Tyamara had been admitted to hospital four weeks ago suffering from abdominal tuberculosis (TB) and a liver condition, his manager Anele Hlazo said.
He took a turn for the worse on Monday and was moved to ICU and put on life support.
"We got the call just after 1am this morning. We are all shocked. We never expected this to happen. The family is taking it very hard."
His death comes a day after a night vigil was held at Central Methodist Church in Johannesburg CBD to pray for his recovery. Condolences for his passing have been pouring in over social media since news broke in the early hours on Friday.
Johannesburg mayor Herman Mashaba tweeted: "Deep condolences to the family of gospel singer and star Lundi Tyamara who passed on earlier. May his soul rest in peace."
Veteran entertainment journalist Lesley Mofokeng said: "He put up a good fight. He ran his race and now belongs to the ages. Rest in perfect peace Lundi Tyamara."
The family was yet to announce plans for a funeral.
Tyamara's death follows that of another gospel legend, Sfiso Ncwane, who died last month aged 37 after a short illness with kidney failure.