Mohammed and four co-accused were in court Saturday to be arraigned, clearing the way for a long-delayed, high-profile trial of the men charged with plotting the September 11, 2001 attacks.
Dubbed "KSM," Mohammed was regarded as one of Al-Qaeda chief Osama bin Laden's most trusted and intelligent lieutenants before his March 2003 capture in Pakistan. He then spent three years in secret CIA prisons before arriving in Guantanamo in 2006.
He was known as "mukhtar" (the chosen one) or "the brain" in extremist circles, but mocked as "KFC" for his love of fried chicken, biographers say. An "arrogant," "very proud" man of small stature, Mohammed also had a reputation for being short-tempered.
The 47-year-old trained engineer was involved in a whole string of major plots against the United States, where he attended university.
In addition to planning the operation to bring down the Twin Towers, Mohammed claims to have personally beheaded US journalist Daniel Pearl in 2002 with his "blessed right hand" and to have helped in the 1993 World Trade Center bombing that killed six people.
Among several failed plots he admitted to interrogators were planned assassinations of the late pope John Paul II and former US presidents Bill Clinton and Jimmy Carter.
Mohammed was born on April 24, 1965 to a Pakistani family living in Kuwait but his roots lie in Baluchistan, a restive Pakistani region bordering Afghanistan.
He says he joined the Muslim Brotherhood, an anti-Zionist activist group, when he was 16, beginning a life-long infatuation with violent jihad.
In 1983, Mohammed moved to the United States for his studies and graduated from North Carolina Agricultural and Technical State University with a degree in mechanical engineering three years later.
During his stay in the United States, he stayed with a "small group" of Arabs from Kuwait, biographer Richard Miniter told AFP.
"KSM's limited and negative experience in the United States -- which included a brief jail stay because of unpaid bills -- almost certainly helped propel him on his path to becoming a terrorist," a US intelligence summary said.
"He stated that his contact with Americans, while minimal, confirmed his view that the United States was a debauched and racist country."
In 1987, he traveled to Afghanistan and fought alongside mujahideen rebels against the Soviet invasion. He stayed in Afghanistan until 1992, and then headed to Bosnia and Herzegovina to fight with Muslim fighters against the Serbs, according to the 9/11 Commission report.
It was not until a botched 1995 plot to blow up US airliners over the Pacific, known as Operation Bojinka, that he achieved notoriety.
Mohammed was safely out of reach in Qatar by the time the Philippine authorities unraveled the plot, believed to have marked the first time he helped plan an attack.
He had earlier helped finance the 1993 World Trade Center bombing hatched by his nephew Ramzi Youssef that killed six people and injured over a thousand.
Mohammed fought with bin Laden in Afghanistan in the late 1980s, but they only forged a close relationship 10 years later and Mohammed then allegedly began plotting what would later become the September 11, 2001 attacks.
"Bin Laden realized that this difficult little man was absolutely essential for turning AQ into the kind of organization he wanted," Miniter said.
Mohammed then had a hand in nearly every single Al-Qaeda plot until his arrest. But experts say it is not possible that one man alone was at the center of all these terror plans.
"He's obviously a smart guy, but he's not a genius... He didn't do the impossible," said Terry McDermott, who authored "The Hunt for KSM" with Josh Meyer.
Most of what is known about Mohammed comes from interrogation transcripts released by the Pentagon and there are bound to be questions at the Guantanamo courtroom over the harsh procedures used to obtain that information.
He is known to have been waterboarded 183 times during his years in US custody. Rights groups denounce the simulated drowning technique as torture.
In reported confessions, Mohammed claimed to be the "military operational commander" for all Al-Qaeda foreign operations, saying "I'm not making myself a hero."
"I'm looking to be a martyr for long time," he told a hearing at Guantanamo in June 2008, the first time he had appeared in public since his arrest.
Photos released by the US military at the time showed a wild-eyed, disheveled man in a white T-shirt, but he appeared in court Saturday sporting a long, flowing beard. It marked his first public appearance in three years.