John Githongo said he "was no longer able to continue serving the government of Kenya" but gave no further reason for his departure as governance and ethics permanent secretary.
He was recruited in January 2003 from the anti-corruption non-governmental organisation Transparency International, to help President Kibaki's new administration tackle the fraud that became endemic under the 24-year rule of the former president, Daniel arap Moi. Privately, Mr Githongo told critics that his success in the clean-up should only be judged after two years in office.
Two years later, the country still remains close to the bottom of international corruption clean-up league tables. His exit is the latest blow to the government of Mwai Kibaki, which was elected in December 2002 on an anti- corruption ticket.
Donors have repeatedly warned that the country risks losing vital aid cash if it cannot clean up its accounts. Last night, Sir Edward Clay, British High Commissioner to Kenya and a persistent critic of the government's record, said Mr Githongo's resignation left a "large hole" in its anti- corruption efforts.
"Personally I respect John Githongo as a person of integrity, courage and principle," he said. "He was intensely committed to the patriotic task of clearing corruption out of government." Last week, Sir Edward reignited the debate over sleaze, launching an outspoken attack on progress so far.
He accused government officials of colluding with members of the previous Moi regime in milking cash from procurement deals. "We are not talking about minor corruption. We are talking about massive looting and/or grand corruption which has a huge impact on Kenya's economy," he said.
Sir Edward, who caused a similar furore with stronger language last July, said he had handed a dossier of 20 corruption cases to the government.
Other ambassadors echoed Sir Edward's criticisms. The US ambassador, William Bellamy, said corruption was costing the country millions in cash that should be used to fight Aids.
Many donors remain nervous that, without stronger guarantees, they cannot be sure where their money is going. They estimate sleaze has cost the country $1bn (pounds 550m) in the past three years - about a fifth of this year's budget.
The appointment of Mr Githongo was one of President Kibaki's first moves as he attempted to put his manifesto into action. His election ended the 24-year reign of Daniel arap Moi and brought the prospect of winning back lost foreign aid.
Mr Githongo, a former journalist, had previously led the Nairobi office of Transparency International. There were some signs of progress, with Kenya winning plaudits from Transparency International in its annual report last year.
The International Monetary Fund also resumed lending to the country after a four-year suspension. However, the Transparency International report still ranked Kenya 129 out of 144 countries last year and corruption officials are unable to point to a single high-profile conviction. Gladwell Otieno, who replaced Mr Githongo as the country's director of Transparency International, said that his departure was a blow for Kenya.
"If he has quit it is because there is nothing that can be done about corruption. Obviously, it has become apparent to him that there is no political commitment in the fight against corruption that would make a difference," she said.
Dr Alfred Mutua, a government spokesman, paid tribute to the work of Mr Githongo but added that Sir Edward's criticisms were nothing new.
"Almost all these contracts involved British companies working with unscrupulous Kenyans to rob Kenya blind," he said.
"When we have told development partners of where we are, and how we are conducting an internal audit, they are satisfied. Clay just comes up with the same old cases that we already know and pretends it is a new issue."