On Saturday, Misuzulu will enter the "cattle kraal" at the Zulu royal residence or KwaKhethomthandayo in Nongoma, a small town in the ethnic group's southeastern heartland province of KwaZulu-Natal.
There, he will take part in a secret rite designed to present the new monarch to his legendary ancestors.
Afterwards, he will be introduced to his people, who will pledge to "accept the king as their king", said Gugulethu Mazibuko, an expert in African cultures at the University of KwaZulu-Natal.
Only selected members of the royal family and Zulu warriors, known as amaButhos, are allowed to witness the kraal rite up close, but large crowds are expected to gather at the royal palace to celebrate the event.
King Zwelithini left behind six wives and at least 28 children when he died last year at the age of 72 after a battle with diabetes-related illness.
Misuzulu is the first son of Zwelithini's third wife, Shiyiwe Mantfombi Dlamini, whom the late monarch named in his will as regent after his death.
She left a will that designated Misuzulu to ascend to the throne -- a development that did not go down well with other branches of the family.
The new monarch's first name means "strengthening the Zulus." Yet his path to the crown has been the subject of an acrimonious family dispute.
After a failed legal bid to challenge the succession, Prince Simakade Zulu, the son of the late king's first wife, surrounded by a small group of people, underwent the cattle kraal rite last weekend, in a last-ditch move thwart Misuzulu's coronation.
Zwelithini enjoyed the trappings of his royal status, receiving some 71 million rand ($4.2 million) a year from the government to run royal affairs and fund a lavish lifestyle.
He owned several palaces and other properties, with a royal trust managing almost three million hectares (7.4 million acres) of land -- an area about the size of Belgium.
In exchange the king serves as guarantor of social peace, said Sihawukele Ngubane, a specialist at the University of KwaZulu-Natal.
"He caters for the welfare of his subjects," she said, explaining royals are in charge of community and infrastructure development on the land managed by the trust.
Zulu kings are descendants of King Shaka, the 19th-century leader still revered for having united a large swathe of the country as the Zulu nation, which fought bloody battles against the British colonizers.
After Saturday's rituals, the coronation process will be completed at another ceremony presided by South African President Cyril Ramaphosa set to take place in the coming months.