Amano led the International Atomic Energy Agency (IAEA) since 2009 and was planning to step down in March 2020 because of an unspecified illness.
In a statement, the IAEA secretariat expressed its "deepest sadness" at the passing away of the Japanese diplomat.
"The secretariat wishes to share his most recent reflection which he intended to include in his letter to the Board of Governors announcing his decision to step down," said the statement.
The agency released part of Amano's letter in which he was quoted as saying that he was "very proud of our achievements and grateful to member states and agency staff".
"During the past decade, the agency delivered concrete results to achieve the objective of 'Atoms for Peace and Development', thanks to the support of member states and the dedication of agency staff," said Amano, according to the agency.
Amano had overseen a landmark nuclear deal between Iran and six major world powers in 2015 that restricted the Islamic republic's uranium enrichment programme.
The agency said the flag over its head office in Vienna had been lowered to half-mast.
Amano had taken over from Mohamed ElBaradei a decade ago and his third term was due to run until November 2021. But, diplomatic officials in Vienna said that he was planning to communicate to the agency's board of governors his decision to resign in March, Efe news reported.
He was regarded as more reserved and technocratic than his outspoken predecessor, who regularly clashed with US officials over its policies on Iran.
Amano joined the Japanese Foreign Ministry in 1972 and held increasingly senior positions, notably as Director of the science division and Director of the nuclear energy division.
He served as Chairman of the IAEA's policy-making board of governors in 2005-06 when the agency and ElBaradei were jointly awarded the Nobel Peace Prize.
Amando was narrowly elected as the agency's head in 2009, backed by Western powers, in an election race that highlighted a deep divide between industrialized and developing nations on the IAEA's board, the BBC reported.
It is not yet clear who will succeed him, though discussions over who will replace him began last week.
( With inputs from IANS )