Mohammed has claimed to be the operational mastermind behind the September 11, 2001, attacks in the US.
Abu Zubaydah is alleged to have been an aide to Osama bin Laden, the al-Qaeda leader, while al-Nashiri is said to have been the operational commander of the suicide attack on the USS Cole in Yemen in 2000.
All three men were initially held and interrogated at secret CIA-run detention centres overseas before being transferred in 2006 to Guantanamo Bay.
Hayden said that simulated drowning, which critics say is tantamount to torture, was used five years ago, at a time when further catastrophic attacks on the United States were believed to be imminent.
"The circumstances are different than they were in late 2001, early 2002," Hayden said.
Congress is considering banning the technique.
Hayden defended the use of coercive interrogation techniques as lawful and said he opposed moves by Congress to make the agency follow rules of interrogation set forth in the army field manual.
Michael Mukasey, the attorney-general, told Congress last week that the CIA no longer uses "waterboarding" and that it was not "currently" an authorised interrogation technique.
However, he refused to say whether waterboarding was torture.
"There are some circumstances where current law would appear clearly to prohibit waterboarding's use. Other circumstances would present a far closer question," he said.