Dr. Sampurnanand took active participation in the Non Cooperation Movement that was led by Mahatma Gandhi and supported by the Indian National Congress Party. He was also the editor of a Hindi monthly journal titled Maryada, which was staffed by Pandit Madan Mohan Malaviya in Benaras. Dr. Sampurnanand frequently contributed to the National Herald and the Congress Socialist Party of India. He was elected to the All India Congress Committee in the year 1922 and was appointed as the provincial Minister for Education in the Uttar Pradesh cabinet. After the nation achieved independence from the rule of the British Empire in India and the Partition of India, Sampurnanand was appointed as the Education Minister in the first popular government of the state of Uttar Pradesh. During his tenure, he devised plans for the establishment of an astronomical observatory, including a Time unit, at the Government Sanskrit College (GSC) in Benaras, which is presently known as Sampurnanand Sanskrit University (Sampurnanand Sanskrit Vidyalaya).
Later Dr. Sampurnanand became the Federal Minister from the year 1946 to 1951. He held portfolios such as finance, education and home labour from 1951 to 1954. Eventually Sampurnanand was elected as the Governor of Rajasthan on April 1962. He served in office till May 1967. Sampurnanand was also appointed as the first Chairman of State Lalit Kala Akademi in Uttar Pradesh, which was founded on 8 February 1962 as a fully funded self-governing unit, under the Department of Culture, Government of Uttar Pradesh.
Dr. Sampurnanand died on 10th January 1969 in Varanasi, Uttar Pradesh. The appointment of Sampurnanand as the Chief Minister of Uttar Pradesh and the Governor of Rajasthan indicated a modern beginning of Indian politics.