US Ambassador to India, Nancy Powell, has submitted her resignation to President Barack Obama and will return to the US before the end of May.
The announcement was made in a statement issued on the embassy's website on Monday. Her retirement move, back to her home in Delaware, has been "planned for some time".
Powell arrived in New Delhi in April 2012 and was the first female US ambassador to India. She ends a 37-year career that has included postings as ambassador to Uganda, Ghana, Pakistan and Nepal and India.
Relations between the US and India were tested after the arrest of an Indian diplomat in New York last December, but appear to have improved in recent months.
In February Powell met Gujarat Chief Minister Narendra Modi, the Bharatiya Janata Party's (BJP) prime ministerial candidate in this month's elections.
Their meeting, in Gujarat's capital of Gandhinagar, marked the end of Washington's decade-long boycott of the controversial Indian politician.
In 2005 the US in 2005 revoked a visa for Modi under a domestic law that bars entry by any foreign official seen as responsible for "severe violations of religious freedom".
Last month, a senior State Department official indicated the US was ready to do business with Modi should he win the elections.