Powell, 67, who announced ending of her tenure in India in March, would be replaced temporarily by Kathleen Stephens, the former US ambassador to South Korea.
Stephens will serve as the charge until a new permanent ambassador is nominated and confirmed by the US Senate, State Department Spokesperson Jen Psaki told reporters.
Obama has not nominated anyone for this important diplomatic posting.
Stephens is expected to arrive in New Delhi early June.
"Ambassador Nancy Powell will depart New Delhi on Thursday, May 22, following her March announcement of her retirement," Psaki said.
"Powell departs India with the deep appreciation of the administration and the State Department for her outstanding work as ambassador to India. Under her guidance we continued our strategic partnership across a number of important areas such as trade, defence, space and education," she said.
Psaki said Powell is concluding a distinguished 37-year career that has also included postings as US ambassador to Uganda, Ghana, Pakistan and Nepal, as well as service in Canada, Togo, Bangladesh and Washington, where she was most recently director general of the Foreign Service.
"We offer our profound gratitude for Ambassador Powell's dedication and her inspiring career in public service and wish her all the best in her retirement," the State Department spokesperson said.
"Ambassador Kathleen Stephens will serve as the charge until a new permanent ambassador is nominated and confirmed by the Senate," Psaki said.
"Stephens is a career foreign service officer with the rank of career minister. She was US ambassador to South Korea from 2008 to 2011 and previously served in senior positions in Washington, Asia and Europe. She will arrive in Delhi in early June and look forward to working closely with the new government of India on a range of issues," Psaki said.
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