Swiss Judge Laurent Kasper-Ansermet announced his resignation through a statement issued on his behalf by the Extraordinary Chambers in the Courts of Cambodia, the tribunal upon which he is sitting.
Kasper-Ansermet criticized his fellow judge, Cambodian You Bunleng, for refusing to discuss cases 003 and 004 where former senior Khmer Rouge leaders are scheduled to be on trial for their parts in mass killings in the late 1970s.
The ECCC statement said You Benleng "issued a written order to Judge Laurent Kasper-Ansermet, demanding that he immediately cease his 'unlawful activity.' This ultimatum was reiterated last week."
The result of the ultimatum is "interference with the administration of justice" and Kasper-Ansermet "considers that the present circumstances no longer allow him to properly and freely perform his duties."
Kasper-Ansermet will step down May 4, although he won't initiate any new investigations up to then, the ECCC said.
Kasper-Ansermet arrived in Cambodia in early December to replace an outgoing German judge, Siegfried Blunk. Blunk and You Bunleng were heavily criticized by Human Rights Watch for not being impartial.
But a month later, he had his first open clash with You Bunleng, the BBC reported at the time.
Kasper-Ansermet said he was unable to provide updates on the progress of investigations because his Cambodian counterpart, You Bunleng, would not agree to it.
You Bunleng responded, saying Kasper-Ansermet was not yet legally accredited and lacked understanding of the legal principles of the tribunal's work.
The tribunal was set up in 2006 but it wasn't until 2010 that it sat for the first time.
It finally confirmed a 35-year jail sentence to S21 Khmer Rouge prison boss Kaing Guek Eav, 67 also known as Duch.
He admitted to overseeing the torture and deaths of around 14,000 people -- including children -- at the prison.
Duch, whose case was trial 001, earlier this month agreed to testify for the prosecution in case 002 which began in November.
On trial are Nuon Chea, deputy leader to Pol Pot and who was known as Brother Number Two in the brutal Khmer Rouge regime.
Nuon is accuses of leading the Year-Zero plan, a mass forced migration of people from cities to work as peasants on communal farms in the countryside during the four-year regime.
The policy included the abolition of money and private property, as well as banning religion in the country the Khmer Rouge called Democratic Kampuchea.
Several million people are believed to have starved to death or killed in what became known as the Killing Fields.
An invading Vietnamese army eventually overthrew the regime whose leaders and cadres, including Pol Pot, fled into the jungle where they remained for years.
Nuon is joined in the dock by Khieu Samphan, the Maoist regime's former head of state, and Ieng Sary, its former foreign minister, all in their 80s.
During questioning this week, Duch described that his immediate superiors instructed him in interrogation methods, the Voice of America said.
Duch said he was shown how to apply electrical wire to bodies, methods of water-boarding and suffocation.
The defendants pleaded not guilty.
The regime's most wanted man was Pol Pot who was captured in 1997 but died while under house arrest in 1998.
Although not proved, it's been suggested that Pol Pot either was poisoned or committed suicide.