Justice Minister Piet Hein Donner and Housing Minister Sybilla Dekker announced their resignation in a short declaration to parliament after the report was released.
The report concluded that their ministries were partly to blame for the deadly outcome of the blaze in the detention centre that left 11 illegal immigrants dead in October 2005.
"Ministerial responsibility means that in the eyes of the victims I represent the departments whose actions are said to have contributed to their suffering... It is for me to show that this is not without consequences," Mr Donner said.
In its report, the independent Dutch Safety Board said that "there would have been fewer or no victims if fire safety had gotten the attention of the authorities involved".
"The (justice ministry) is the primary responsible party... They are responsible for the safety of their employees and the people that are detained," said the board, chaired by Pieter van Vollenhoven, brother-in-law to Queen Beatrix.
It added that the housing ministry, which oversaw the detention centre's construction, had also failed because the site did not comply with the government's own fire safety rules.
Fire ‘deliberate’
In October last year nine men and two women died trapped in their cells when fire broke out in a wing of the prefabricated detention centre designed to hold some 400 people.
They were from Bulgaria, the Dominican Republic, Georgia, Libya, Romania, Surinam, Turkey and Ukraine.
Fifteen people were injured. A total of 298 inmates were being held in the jail, which is located on the grounds of Schiphol airport, at the time.
All the people who perished that night were considered to be illegal immigrants awaiting deportation from the Netherlands.
The fire was set off by a stray cigarette butt, the report said without commenting on whether it was accidental or intentional.
The public prosecutor's office suspects a Libyan detainee, identified in the Dutch press as Achmeon d Al-Jeballi, started the fire deliberately.
’Harsh and clear’
Dutch Prime Minister Jan Peter Balkenende said the safety board's conclusions were "harsh and crystal clear".
"I have great respect for the decision the ministers took," he added.
The resignations are largely symbolic as political commentators said it would have little effect on the current centre-right government, which faces a legislative election on November 22.
Mr Donner and Ms Dekker, who will not be replaced as the election is so close, said that had they not stepped down, the parliamentary debate on the Schiphol fire report would probably focus only on whether or not they would resign.
A date for the parliamentary debate will be set after the government issues an official response to the report, which Mr Balkenende said would come as soon as possible.