Khalid Sheikh Mohammed, the self-proclaimed architect of the 9/11 attacks, has been formally charged with attacking the US, along with four others.
The Pentagon said that Mohammed, 48, is being held at camp 7 in Guantanamo Bay and will appear at a military commission hearing in May.
A military trial is expected to start by the beginning of next year, ending years of debate over whether the defendants should face a military or civilian court.
Also on trial will be Walid bin Attash, Ramzi bin al-Shibhi, Ali Abd Aziz Ali and Mustafa Ahmed al-Hawsawi.
Attash is accused of training two hijackers at an al-Qaida camp. Shibhi allegedly acted as the link between hijackers and al-Qaeda leaders. Ali is believed to have transferred funds to operatives and Hawsawi allegedly arranged funding.
The charges include conspiracy, attacking civilians, serious bodily harm, murder, hijacking an aircraft and terrorism.
The US confirmed it will seek death penalty. The defendants will be tried jointly as they are all accused of playing a key role in the attacks.
Profile of 9/11 Architect
Khalid Sheikh Mohammed, known simply as "KSM" by US officials, comes from Pakistan but was raised in Kuwait. At the age of 16 he says he joined the Muslim Brotherhood.
He moved to the US for his studies and graduated from North Carolina Agricultural and Technical State University with a degree in mechanical engineering.
In the mid-80s he travelled to Afghanistan and fought with the Afghani Mujahidin against the Soviet invasion.
Ten years later he was allegedly involved in Operation Bojinka, a botched plot to blow up US airliners between the US and Asia.
He fled to Qatar but his involvement in the failed plot is said to have brought him closer to Osama Bin Laden and ultimately led to his pivotal role in the 9/11 attacks on the World Trade Centre in New York and the Pentagon.
Mohammed acted as one of al-Qaida's most trusted intelligence lieutenants until he was arrested in March 2003 in Pakistan.
He was rapidly handed over to the American authorities and held in a secret prison for three years before being transferred to Guantanamo in 2006.
He allegedly told interrogators he planned the attacks "from A to Z" and reportedly admitted he beheaded US journalist Daniel Pearl in 2002 as well as being involved in other anti-American plots.
Sceptics say Mohamed's confessions may have been prompted by torture including waterboarding. He is said to have been subjected to simulated drowning 183 times by CIA operatives during his years in US custody.
During a hearing last year Mohammed indicated he would plead guilty and said he would welcome martyrdom.