Khalid Sheikh Mohammed, appearing in public for the first time since his capture in Pakistan in 2003, refused the help of lawyers to defend him.
He told the court he wanted the death sentence sought by the prosecution as he wished to become a martyr.
Correspondents says the hearing raises questions about military commissions.
The five men, dressed in white tunics and turbans, did not have to be forced out of their cells, as some defendants in earlier hearings have been, Reuters news agency reports.
Marine Col Ralph Kohlmann, presiding over the hearing, told Khalid Sheikh Mohammed he faced the death sentence if convicted.
"That is what I want, I'm looking to be a martyr for long time," Khalid Sheikh Mohammed replied.
The US describes Khalid Sheikh Mohammed, believed to have been al-Qaeda's third in command, as "one of history's most infamous terrorists".
Waterboarding
Following his arrest he was held at a CIA secret prison, where he was subjected to harsh interrogation techniques and a practice known as waterboarding, that simulates drowning, until he was moved to Guantanamo Bay two years ago.
The US military says that as well as admitting involvement in the 11 September 2001 attacks on Washington and New York, he has confessed to being involved in more than 30 terrorist plots around the world, including plans to attack London's Big Ben and Canary Wharf.
He is one of five so called "high value detainees" appearing at hearing.
The other suspects are:
Ramzi Binalshibh, a Yemeni man described by the US as the co-ordinator of the 9/11 attacks, who, according to intelligence officials, was supposed to be one of the hijackers, but was unable to get a US visa
Mustafa Ahmad al-Hawsawi, a Saudi man said by US intelligence officials to be one of two key financial people used by Khalid Sheikh Mohammed to arrange the funding for the 11 September hijackings
Ali Abd al-Aziz Ali, also known as Amar al-Balochi, who is accused of serving as a key lieutenant to Khalid Sheikh Mohammed - his uncle - during the 11 September plot
Walid Bin Attash, a Yemeni national who, according to the Pentagon, has admitted masterminding the bombing of the American destroyer, USS Cole, in Yemen in 2000, which killed 17 sailors, and is who is accused of involvement in the 11 September 2001 attacks
The charges against them list "169 overt acts allegedly committed by the defendants in furtherance of the September 11 events".
The charges, which include 2,973 individual counts of murder - one for each person killed in the 9/11 attacks - are the first directly related to the 9/11 attacks to be brought against any Guantanamo inmates.
The five are among 19 prisoners due to face the military tribunals, which were set up in the wake of 9/11 to try non-US prisoners who have been classed as "enemy combatants" by the White House and therefore deemed to not be entitled to the legal rights normally afforded to prisoners.
Justice in the dock
The trials have already raised questions about not just the treatment of detainees, but also the legitimacy of American military commissions.
The BBC's Jonathan Beale - one of 60 international journalists attending the trial - says these trials will be as much a test case as a showcase of military justice.
The US authorities say they have bent over backwards to make sure that the trials are fair but some of its own lawyers have already condemned the process as fundamentally flawed.
US air force Brigadier General Tom Hartmann told the Associated Press news agency that the tribunals would allow the detainees the chance of a proper hearing.
