[5][6] He was born in Hindu Brahmin family[7] on 29 September 1928 to Dwarka Prasad Mishra, who was a former Chief Minister of Madhya Pradesh.

After Brajesh Mishra, the post of principal secretary became such a powerful one that it eclipsed the status of cabinet ministers.

[16] His batch as an Indian Foreign Service officer was the same as the Indian Administrative Service batch of K. Subrahmanyam, widely considered as the doyen of India's strategic affairs community, and made him the first convener of the National Security Advisory Board where they worked closely on many issues.

He was closely involved in planning the 1998 Nuclear tests and played a crucial role in shaping India's policy regarding Pakistan and China.

After demitting office, Mishra had initially expressed reservations against the Indo-US civilian nuclear deal.