In 1955, Ong's foray into politics began as a polling agent for Lee Kuan Yew in the 1955 legislative assembly election. In 1956, Lee wrote to Ong and offered him a job as party organising secretary for the PAP. He stood for election in the 21 December 1957 for the fully elected City Council of Singapore as a candidate for the Tanjong Pagar ward and was successfully returned and became the first and only ever Deputy Mayor. He held the post until he resigned in April 1959 to contest the Legislative Assembly election as the PAP's candidate for Telok Ayer. This was to be the first Legislative Assembly in which all seats were elected. He won the seat, which he retained till his retirement in 1984. He was subsequently appointed as Minister for Home Affairs in the first self-government Cabinet and played a key role to eradicating yellow culture and crime in Singapore society. His cabinet appointment also made him part of the Internal Security Council which sanctioned Operation Coldstore in 1963. From 1963 to 1970, Ong took on the highly sensitive Education ministerial portfolio at a time when Chinese language culture and education issues were highly politicized. By increasing the teaching of English in Chinese schools and vice versa, he was instrumental in laying the foundation for the bilingual policy for which Singapore is famous. In 1970, Ong became the Labour Minister. In 1980, he took over as the Environment Minister. In 1984, he stepped down from the Cabinet to make way for younger leaders. However, he displayed some unhappiness at the pace and manner by which he was sidelined from the political scene. He retired from politics in 1988 when his constituency of Telok Ayer was eliminated in the 22 December 1984 general election. Lee recognised Ong's displeasure in a public letter of appreciation: Ong is considered as one of the 'Old Guard' - the first generation of leaders of independent Singapore. He is the sole remaining living member, after Jek Yeun Thong's passing in June 2018.
Philanthropic work
Ong continued to serve the society through his involvement in the community. Ong, who previously served as the vice-chairman of Singapore Hokkien Huay Kuan in the 2000s, is currently serving in the Board of Governors of the association.