He is a senior leader of the AIADMK political party and was a staunch loyalist of former chief minister of Tamil Nadu and AIADMK General Secretary J. Jayalalithaa. His first two terms as Chief Minister came when he replaced Jayalalithaa in the role, after she was forced to resign by the courts. His third term began following Chief Minister Jayalalithaa's death and ended two months later, Edappadi K. Palaniswami was appointed as the Chief Minister by Tamil Nadu Governor C. Vidyasagar Rao. He was sworn in as the Deputy Chief Minister of Tamil Nadu on 21 August 2017. He also holds portfolios of Finance, Housing, Rural Housing, Housing Development, Slum Clearance Board and Accommodation Control, Town Planning, Urban Development, and Chennai Metropolitan Development Authority. On 4 January 2018, O. Panneerselvam elected as Leader of the House in Tamil Nadu Legislative Assembly.