Sandhu, 63, hails from a distinguished family of reformists and educationists in Amritsar, Punjab. His grandfather, Teja Singh Samundri, was a leading figure in the early 20th-century Gurdwara Reform Movement, which reformed the management of Sikh religious institutions. In his honour, the Shiromani Gurdwara Parbandhak Committee (SGPC) hall in Amritsar bears his name.

An accomplished academic, Sandhu's father was a scholar, and his mother, Dr Jagjeet Kaur, earned a doctorate in the United States before serving as Principal of the Government College for Women, Amritsar. Sandhu studied at The Lawrence School, Sanawar, and later at St Stephen's College, Delhi, where he read history. He went on to complete a master's degree in International Relations from Jawaharlal Nehru University before joining the Indian Foreign Service in 1988.

Over a diplomatic career spanning nearly three decades, Sandhu developed particular expertise in India-US relations. He served twice at the Indian Mission in Washington DC, including as Deputy Chief of Mission from July 2013 to January 2017. Earlier, he was First Secretary (Political) at the Embassy of India, Washington DC, from 1997 to 2000, responsible for liaising with the US Congress. He also served at India's Permanent Mission to the United Nations in New York from 2005 to 2009.

Before his Washington posting as India's Ambassador, Sandhu was High Commissioner to Sri Lanka from January 2017 to January 2020 and had previously headed the Political Wing at India's High Commission in Colombo. He is married to Reenat Sandhu, herself a career diplomat who has served as India's ambassador to Italy and the Netherlands.