Carlos Mazon has faced calls to resign, including from victims' relatives, since the October 29, 2024, downpour killed 229 people and caused billions of euros in damages, mainly in suburbs south of Valencia, Spain's third-largest city.
"I can't go on any more," Mazon, of the opposition conservative People's Party (PP), told reporters on Monday.
"I know I made mistakes, I admit it, and I know I'll have to live with them for the rest of my life."
In a prior speech, he excoriated what he termed insufficient support from Socialist Prime Minister Pedro Sanchez' government.
Sanchez's office did not immediately comment.
Mazon also blamed national weather agency AEMET and the body regulating the regional hydrological network, belonging to Spain's Energy Ministry, for failing to adequately warn of the impending disaster.
The ministry said it would comment later.
Rosa Alvarez, who heads the main association of flood victims, called Mazon's speech "painful and worthless".
"He is still repeating lies and making it look like he's the victim," she told SER radio station.
Mazon did not say if he was calling a snap election, nor clarify whether he was also quitting his seat in the regional assembly - which would end his parliamentary immunity - nor who his interim successor would be.
He said he would have resigned earlier but did not out of duty to lead reconstruction.
Residents of the affected areas accuse the regional government of issuing an alert too late after buildings were already under water and many people were drowning in the worst flood-related event in Europe since 1967.
Experts say successive failures - to conduct flood mitigation work on rivers, better protect houses, educate people and warn residents quickly - added to the fatalities.
Mazon's resignation came on the day Maribel Vilaplana, a journalist with whom he was eating lunch when the floods began, was set to testify as a witness before a judge investigating authorities' potential criminal liability for the deaths.
As Vilaplana arrived at court, victims' relatives shouted: "Tell the whole truth for their sake."
The PP said its national leader, Alberto Nunez Feijoo, would hold a media conference later on Monday.
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