Officials at the tribunal confirmed the arrest and said he would be brought before the tribunal later on Monday to be formally read the charges against him.
No further details were given as to the charges he faces.
War crimes charges
Khieu Samphan's detention had been widely expected, following the arrest last week of Ieng Sary, the Khmer Rouge's ex-foreign minister, and his wife Ieng Thirith, the regime's social affairs minister.
However, his illness and admission to hospital last week had cast doubts on whether he would be considered in a fit state to stand trial.
Ieng Sary and his wife were both charged with crimes against humanity, while Ieng Sary was also charged with war crimes.
The first trials under the much-delayed tribunal are expected to begin next year.
Up to two million Cambodians are thought to have died through starvation, overwork or execution during the regime's 1975-79 rule.
Despite this, no senior member of the Khmer Rouge government has ever faced trial.
Pol Pot, the group's supreme leader and so-called "Brother Number One", died in his jungle hideout in 1998.
In a book published just days before his arrest, Khieu Samphan denied the Khmer Rouge ever intentionally committed mass murder and "always thought about the people's well-being".
The book, titled Reflection on Cambodian History from Ancient Times to
the Era of Democratic Kampuchea," first appeared in markets in Cambodia last week.
In it, for the former head of state writes: "There was no policy of starving the people. There was no policy of mass killings."
On Tuesday the former head of the Khmer Rouge's notorious Tuol Sleng torture and detention centre is due to appear before the tribunal to appeal against his detention.
Kaing Guek Eav, also known as Duch, was detained earlier this year on charges of war crimes and crimes against humanity.
His appearance will be the first public hearing for any former official of the Khmer Rouge.