Alice Nzomukunda, the second vice president, told reporters on Tuesday that she could not "remain indifferent" to troubling developments in the central African country that had only recently been experiencing peace after 12 years of civil war.
She was the second-highest ruling party member of government after the president.
"My decision was motivated by numerous political problems which Burundian people are undergoing - problems of security, of not respecting the law, the management of state finances and of human rights laws which are violated," she said.
"The country was on a good path to overcome all these problems, but corruption and economic embezzlement are undermining it."
Burundi's president, the former Hutu rebel leader Pierre Nkurunziza, took office a year ago through a UN-backed plan amid optimism after the end of years of brutal ethnic violence that began after the assassination of the country's first democratically elected Hutu president in 1993.
But recently western diplomats have criticised the government, for its handling of an alleged coup plot in which a half-dozen suspects, including the former president, Domitien Ndayizeye, have been arrested.
"The country was on a good path to overcome all these problems, but corruption and economic embezzlement are undermining it"
Alice Nzomukunda, second vice president
Burundi says it has evidence of the coup plot, and dismisses complaints by human rights watchdogs that it is cracking down on free expression through its arrests of opposition, civil rights and anti-corruption activists since May.
A government spokesman could not immediately be reached for comment.
Nzomukunda has been a critic of the government for some time and there were rumours she was to be fired soon.
Last month her house was hit in a mortar attack with the government blaming the National Liberation Force, although only government forces have access to the type of mortar used.
Burundi, a small nation of seven million people reliant on the growth of tea and coffee has suffered from cycles of ethnic slaughter between majority Hutus and the dominant Tutsi minority since independence from Belgium in 1962.