After graduation, he helped out at his father’s company, and later founded the Kuok Brothers Sdn Bhd in 1949. He began investing in the sugar refinery business and became known as the "Sugar King" of Malaysia.

Robert Kuok is a shrewd, business savvy and well connected businessman. He has formed many strategic alliances with various parties. With governments, he formed joint ventures to establish shipping businesses, and hotels, office buildings and convention centres. With business partners, he created banks and financial services. Thus, through business acumens, creativity and his valuable political connections, he has diversified into many important sectors of the economy. Apart from a multitude of enterprises in Malaysia, his companies have investments in many countries like Singapore, Thailand, Mainland China, Indonesia, Fiji and Australia. His business interests range from sugarcane plantations, sugar refinery, four milling, animal feed, oil and mining to finance, hotels, properties, trading and freight.

Kuok controls the Shangri-La Hotels and Resorts Chain, Kerry Group, Perlis Plantations Bhd, South China Morning Post and dozens of other companies. Nowadays, Kuok Khoon Ean one of Robert's sons, handles most of the day-to-day operations of his businesses.