Natesa Mudaliar was born in Triplicane, Madras in 1875. He had his early schooling in Madras and graduated in arts from the University of Madras. Natesan worked as a lecturer in Pithapuram Maharaja College and as an interpreter in the Gordon Woodrof Company. He graduated in medicine from Madras Medical College and practised as a doctor. In 1914, he started a hostel for non-Brahmin students in Madras Presidency. This marked his entry in South Indian politics.
In 1912, the Madras United League was formed. Natesa Mudaliar was one of the founders of the league and served as its Secretary. The league was largely composed of government employees and concentrated on improving the literacy of non-Brahmins by conducting adult education classes. In 1914, the Madras United League was renamed as the Madras Dravidian Association and Panaganti Ramarayaningar, later the Raja of Panagal was elected President. As a part of its programme, the Madras Dravidian Association conducted a hostel called "Dravidian Home" for the benefit of non-Brahmin students. Natesan was the caretaker of this hostel.
Through the mediatory efforts of Mudaliar, political opponents Sir Theagaroya Chetty and Dr. T. M. Nair came together and resolved to put forth their efforts to form an organization representing the non-Brahmins of the Madras Presidency. In November 1916, at a non-Brahmin conference presided over by Panaganti Ramarayaningar, the four important non-Brahmin organizations in the Presidency came together to form the South Indian Liberal Federation, more popularly known as the Justice Party. Theagaroya Chetty became the first President of the federation. Natesa Mudaliar, along with Theagaroya Chetty, was instrumental in negotiating an end to the Buckingham and Carnatic Mills strike of 1921, organized by V. Kalyanasundaram.
Natesan did not participate in the first general elections in Madras Presidency held in 1920. However, in the 1923 assembly elections, Natesan was elected to the Madras Legislative Council. He had differences with ministers in the Raja of Panagal ministry and often criticized the government. When P. Subbarayan took over as Chief Minister, Natesa Mudaliar praised Subbarayan and the Swarajya Arty and appealed for the merger of the Justice Party with the Indian National Congress. At the Non-Brahmin confederation in Coimbatore in 1927, he led the split of the Justice Party into two camps: Ministerialists and Constitutionalists and functioned as the leader of the Constitutionalists till the two groups merged. In 1929, Natesan presided over the Justice Party conference in which a resolution was passed facilitating the admission of Brahmins in the party. In 1933, Natesan expressed his support to C. P. Ramaswami Iyer when the latter spoke against casteism and proposed a temple entry law in order to remove restrictions on scheduled castes entering Hindu temples.
Natesa Mudaliar was known to be a kind-hearted gentleman and was regarded as the "heart" of the Justice Party. K. M. Balasubramaniam compared him to Mahatma Gandhi in his book South Indian Celebrities. Natesan was also known for his dedication to the Justice Party. His oft repeated phrase was: "The Justice Party is the justest Party, Give that party your support hearty."
