Mr Tsipras held an emergency meeting of his Cabinet in which he accepted responsibility for the tragedy, and attacked the opposition for the “deplorable spectacle” of rejecting any accountability.
Speaking in Athens, he said: “Before the cabinet, and the Greek people, I want to assume full responsibility for the tragedy.
“I regard this as self-evident for the prime minister of a country to do, and I call on you to also assume responsibility, no matter how hard.”
He branded the tragedy as perhaps the “heaviest” moment of his term in office and vowed to honour the memory of the individuals who died.
He said: “This is a difficult moment, perhaps the heaviest of our term in office.
“The dead cannot talk, but the least we can do in their memory is to show respect for the truth.”
Mr Tsipras and his government have come under sharp criticism for their handling of the tragedy, and the prime minister has questioned whether authorities could have done more to prevent the deaths.
He said: “I have mixed feelings of pain, devastation and anguish.
“Anguish as to whether we acted as we should have done, if we responded correctly in these critical hours, and if we could have done anything more to save even one more of the souls who died unjustly.”
A criminal investigation into the cause of the wildfires has now been launched, with Deputy Citizen Protection Minister Nikos Toskas declaring there were “serious” signs of arson.
He said: “We have serious indications of criminal acts, as lots of fires appeared in a very short period of time.”
He noted that “a serious piece of information has led us to opening an investigation” into the cause of the tragedy.
The official nevertheless came under sharp criticism on Friday after he declared that he had found no indication “of grave errors” in the way the disaster was handled.
In the wake of the tragedy, Mr Tsipras has vowed to tackle illegal construction, which he believes exacerbated the spread of the fires and the level of destruction witnessed.
He said: “We will proceed with speed and determination to draw up a national plan which will finally deal with the construction anomalies that go back decades.
“If we need to put bulldozers to work and face confrontation, so be it.
“We are not going to sit back with our arms crossed, taking half-measures, waiting indecisively for the next tragedy.”
Rescue teams are continuing to search the area near the port of Rafina as dozens of people remain missing.
Over 60 people are still being treated in hospital, with 11 in intensive care.