He was born in a rural area of Harding near Port Shepstone, KwaZulu-Natal, South Africa, where he developed a fascination with trains.
Ncayiyana's first attempt to train as a doctor in the 1960s was cut short during his third year at the University of Natal Medical School in Durban due to his anti-apartheid activities.
He then pursued postgraduate training in obstetrics and gynaecology at the New York University School of Medicine and practiced as a specialist obstetrician and gynaecologist in Seattle for 15 years.
He was responsible for selecting the articles to be published and wrote editorials that influenced medical thinking in the country for over 20 years.
In addition to his achievements in medicine and education, Ncayiyana has an obsession with flight and aircraft, having trained as a private pilot and learned to fly single-engine planes.