Khandu was included in the state government as Cabinet Minister for Water Resource Development and Tourism. He won the bye election to his father's constituency uncontestedMukto on 30 June 2011 as an Indian National Congress candidate.
Khandu became a secretary of the Arunachal Pradesh Congress Committee in 2005, and the president of the Tawang District Congress Committee in 2010. He was elected Congress Legislature Party leader on 16 July 2016 replacing Nabam Tuki.
Khandu was re-elected unopposed from Mukto in the 2014 Arunachal Pradesh Legislative Assembly election. Khandu took the oath as the chief minister of Arunachal Pradesh on 17 July 2016 at the age of 37 years following a year long political crisis.
On 16 September 2016, 43 MLAs from the ruling party, under the CM Pema Khandu, defected from Indian National Congress to People's Party of Arunachal, an ally of Bharatiya Janata Party.
In December 2016, Khandu proved majority on the floor of the house with 33 of the People's Party of Arunachalâ€™s 43 legislators joining the Bharatiya Janata Party as the BJP increased its strength to 45 with support of two independents as it had 11 MLAs already.
He became second Chief Minister of Arunachal Pradesh of Bharatiya Janata Party in Arunachal Pradesh after 44 days Gegong Apang led government in 2003.
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