[2] Jaishankar joined the Indian Foreign Service (IFS) in 1977, and during a diplomatic career spanning over 38 years, served in different capacities in India and abroad, including as a High Commissioner to Singapore (2007–2009) and as Ambassador to the Czech Republic (2001–2004), China (2009–2013) and the US (2014–2015).

Jaishankar was one of the officials in the MEA, the Department of Atomic Energy and the Prime Minister's office who played a key role in negotiating the Indo-US civilian nuclear agreement.

He returned to New Delhi, where he worked as a special assistant to the diplomat Gopalaswami Parthasarathy and as undersecretary in the Americas division of India's Ministry of External Affairs, dealing with United States.

He was part of the team that resolved the dispute over the supply of US nuclear fuel to the Tarapur Power Stations in India.

Returning to New Delhi, he served as Director (East Europe) in the Ministry of External Affairs and as press secretary and speechwriter for President of India Shankar Dayal Sharma.

[24] Jaishankar is reported to have helped introduce future Japanese Prime Minister Shinzō Abe to his Indian counterpart, Manmohan Singh.

In this capacity, he was involved in negotiating the US-India civil nuclear agreement and improving defence co-operation, including during relief operations following the 2004 Indian Ocean tsunami.

[41] In Beijing, Jaishankar was involved in improving economic, trade and cultural relations between China and India, and in managing the Sino-Indian border dispute.

[44] Also in 2010, Jaishankar negotiated an end to the Chinese policy of issuing stapled visas to Indians from Jammu and Kashmir.

[46] And in May 2013, he negotiated the end of a stand-off resulting from the encampment by China's People's Liberation Army on Ladakh's Depsang Plains, threatening to cancel Premier Li Keqiang's scheduled visit to India if Chinese forces did not withdraw[47][48] (See also 2013 Daulat Beg Oldi Incident).

[51] He was also involved in improving people-to-people contacts between India and China, promoting events that showcased Indian culture in 30 Chinese cities.

[57] Jaishankar was involved in planning of the Indian Prime Minister Narendra Modi's maiden visit to United States in September 2014, welcoming him upon his arrival and hosting a dinner in his honour for members of the Indian-American community.

[6][7] His appointment came three days before the date on which he would ordinarily have retired and meant the unprecedented termination of Sujatha Singh’s two year tenure as Foreign Secretary.

In October 2020, Jaishankar and the Indian Minister of Defence, Rajnath Singh, met with US Secretary of State Mike Pompeo and US Secretary of Defense Mark T. Esper to sign the Basic Exchange and Cooperation Agreement on Geospatial Cooperation (BECA), which facilitates the sharing of sensitive information and intelligence—including access to highly-accurate nautical, aeronautical, topographical, and geospatial data—between United States and India.

The agreement had been under discussion for over a decade, but previous concerns over information security impelled the United Progressive Alliance (UPA) coalition government to block it.

[68] In response to the dialogue, Chinese spokesperson for the Ministry of Foreign Affairs Wang Wenbin criticised the move and advised Pompeo to "abandon his Cold War mentality, zero-sum mindset, and stop harping on the "China threat".

[71] Jaishankar firmly defended buying oil from Russia even after the sanction by western countries during the 2022 Russian invasion of Ukraine and criticised Europe for double standards.

"[80] In February 2023, American investor and philanthropist George Soros criticised Indian Prime Minister Narendra Modi for his alleged Islamophobia, cronyism and authoritarianism.

[81] Jaishankar dismissed his criticism and said that Soros is a "old, rich, opinionated and dangerous" person who uses human rights as a false pretext for regime change operations.

[82] He condemned the Hamas-led attack on Israel on 7 October 2023 as a terrorist act, but also talked about the plight of the Palestinian people, suggesting a "two-state solution" through "dialogue and negotiation".