Reddy, who had tried to thwart division of Andhra Pradesh by ensuring rejection of the Telangana bill by the legislature, submitted his resignation to Governor ESL Narasimhan, which was accepted.
Flaying the manner in which the decision on Telangana was carried out by Congress and the Centre, Reddy also quit as MLA, capping weeks of public defiance as a result of which he burnt bridges with the party's national leadership.
"My party or my future is not important. My fight is to keep the state united and the people will suffer because of division," he said when asked if he would float a new party.
Speculation was rife that the state may be headed for a spell of President's Rule.
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"I am thankful to Congress for making me Chief Minister. But, I am resigning in protest as they have divided the state and hurt the Telugu people and made their future dark. I am quitting as MLA and the Congress party," he said.
Maintaining that the state was being divided "by throwing all norms to the wind", he lashed out at Congress and BJP, which yesterday supported the passage of Telangana bill in the Lok Sabha, besides TRS, saying they did so in quest of "votes and seats".
"This is not an easy decision...I have taken it with a lot of pain that I could not save (unity of) Telugu people," he told a crowded press conference at his camp office.