An Indian Administrative Service (IAS) officer of the 1967 batch from the Uttar Pradesh cadre, he served as the Principal Secretary to the Prime Minister of India, Narendra Modi from 2014 to 2019.

[9][10] He resigned as member of the Board of Directors of Usha Martin Limited on May 26, 2014 upon being invited to join the PMO under the newly formed Modi government.

[25] On 30 August, Misra quit his position as principal secretary at the PMO, though he confirmed he would continue for a couple of weeks at the request of the Prime Minister.

[26] Post his resignation as principal secretary, Mishra was appointed the chairperson of the executive council of the Nehru Memorial Museum and Library in January 2020.

[27] Nripendra Misra was elected as the chairman of the temple construction committee of the Shri Ram Janmabhoomi Teerth Kshetra Trust in February 2020.