Fifa's independent ethics investigator Michael Garcia has quit in protest over the handling of his report into bidding for the 2018 and 2022 World Cups.
The American lawyer cited a "lack of leadership" at the top of football's world governing body.
Garcia said he lost confidence in the independence of judge Hans-Joachim Eckert, an ethics committee colleague.
Uefa president Michel Platini said: "We wanted all transparency but this is a new failure for Fifa."
The head of European football spoke out as Garcia resigned a day after Fifa's appeals panel rejected his challenge of Eckert's summary of his report.
Garcia said: "It is the lack of leadership on these issues within Fifa that leads me to conclude that my role in this process is at an end."
Fifa president Sepp Blatter said: "I am surprised by Mr Garcia's decision. The work of the ethics committee will nonetheless continue."
The association said in a statement that an acting chairman of the committee would be appointed, pending the election of a successor to Garcia.
Qatar whistleblower Phaedra Al Majid said Fifa's rules are a "farce".
She added: "Not even an extensive, purportedly independent, two-year investigation and report could affect its culture."
Russia won the right to host the 2018 World Cup, while Qatar was awarded the 2022 tournament. Fifa cleared both of corruption despite a series of allegations.
|Analysis: BBC sports editor Dan Roan|
|"Having resigned in protest at Fifa's handling of his investigation into allegations of corruption, Michael Garcia has plunged world football's governing body into more turmoil. The American lawyer's probe into the bidding for the 2018 and 2022 World Cups was meant to restore some trust in an organisation plagued by years of scandal. His decision to quit does exactly the opposite, raising more questions over Fifa's ability to run the game. Last month Garcia disowned a summary of his investigation by Fifa judge Hans-Joachim Eckert, who cleared Russia and Qatar as World Cup hosts. Garcia's appeal was dismissed by Fifa on Tuesday and now he has resigned, questioning the organisation's integrity and leadership in a damning statement. Some may question Garcia's motives, and wonder whether he is trying to distance himself from a discredited organisation to preserve his own political ambitions, but his move certainly piles yet more pressure on Fifa. The news broke as Fifa's top executives gathered here in Marrakech for a crunch meeting. On Friday they will vote on whether to publish Garcia's full findings. But the man himself has not waited for that, and for Fifa closure seems further away than ever."|
Garcia's findings were released as a 42-page summary of the 430-page report.
In his resignation statement, he said: "No independent governance committee, investigator, or arbitration panel can change the culture of an organisation."
Garcia said his submission to the Fifa appeal committee outlined what he called "the most serious failings" of Eckert's response.
"Among other points, the brief explained why, when viewed in the context of the report it purported to summarise, no principled approach could justify the Eckert Decision's edits, omissions, and additions," he said.
Fifa meets in Morocco this week and will decide whether to release a full, redacted copy of Garcia's report.
Jerome Champagne, the former Fifa executive who plans to stand against Blatter for the presidency, said: "Michael Garcia's resignation is a step backwards.
"We needed to know what happened before and after the 2 December 2010 World Cup vote. Today, more than ever, we need to know.
"When will the facts be known fully, transparently and above all without suspicion? When will we be able to start rebuilding Fifa's image?"
Fifa vice president Jim Boyce, Britain's most senior football official, said he was "totally shocked and disappointed" at Garcia's resignation.
"I have said on many, many occasions, the ethics committee was the most important committee formed by Fifa following its reform process," said Boyce.
Prince Ali bin Al Hussein of Jordan, a Fifa vice president, said Garcia's decision to quite was "emblematic" of the challenges faced by the organisation.
"I have tremendous respect for people who take principled positions," said Prince Ali.
|Four years of controversy|
|2 December 2010 - Russia and Qatar are chosen to host the 2018 and 2022 World Cups|
|4 October 2013 - Fifa agrees to set up a taskforce to look into alternative dates for the 2022 World Cup in Qatar|
|1 June 2014 - The Sunday Times alleges that former Fifa vice-president Mohamed bin Hammam paid £3m to football officials in return for support for the Qatari bid|
|5 September 2014 - The report into the 2018 and 2022 World Cup bidding process is submitted to Fifa by Michael Garcia|
|13 November 2014 - Fifa releases a 42-page summary of the Garcia report which clears Russia and Qatar of corruption|
|13 November 2014 - Garcia claims the summary of his own report is "materially incomplete" and contains "erroneous representations"|
|20 November 2014 - Garcia and Fifa ethics judge Hans-Joachim Eckert agree to release the full copy of the report to the organisation's compliance chief, Domenico Scala|
|16 December 2014 - Fifa deems Garcia's complaint against Eckert's summary of his report is "not admissible"|
|17 December 2014 - Garcia quits his role as independent chairman of the Fifa Ethics Committee's Investigatory Chamber|