German Defence Minister Karl-Theodor zu Guttenberg has stepped down after he was found to have copied large parts of his 2006 university doctorate thesis.
Mr Guttenberg, considered until recently a possible candidate for chancellor, has already been stripped of his PhD.
He told a news conference that it was "the most painful step of my life".
Tens of thousands of German academics have written to Chancellor Angela Merkel complaining about his conduct.
The plagiarism scandal led to him being nicknamed Baron Cut-and-Paste, Zu Copyberg and Zu Googleberg by the German media.
But Ms Merkel had continued to stand by him, with her party facing three state elections later this month.
Mr Guttenberg told reporters in Berlin that he was relinquishing all his political offices and he thanked the chancellor for her support, trust and understanding.
"I must agree with my enemies who say that I was not appointed minister for self-defence, but defence minister," he said.
"I was always ready to fight, but have to admit I have reached the limit of my strength."
The chancellor told reporters she was confident he would be able to clear up the problems surrounding his thesis and held out the prospect of his return to government.
"I am convinced that we will have the opportunity to work together again in the future, in whatever form that may take," she said, adding that the former minister had "a unique and extraordinary ability" to relate to people.
A 39-year-old aristocrat popular with the electorate, Karl-Theodor zu Guttenberg is a member of the Christian Social Union (CSU), the Bavarian sister party of the chancellor's Christian Democrats.
He came under pressure after a Bremen University law professor began reviewing his 2006 thesis with the aid of the internet.
Reports emerged of a passage from a newspaper article that featured word for word, and then of a paragraph from the US embassy website being used without attribution.
Analysts then estimated that more than half the 475-page thesis had long sections lifted from other people's work.
Eventually the University of Bayreuth, which had awarded him a doctorate, decided that Mr Guttenberg had "violated scientific duties to a considerable extent".
He had already prompted opposition criticism in December for taking his TV presenter wife on a visit to German troops in Afghanistan complete with a large corps of press photographers.
As his popularity began to wane Mr Guttenberg's political allies began to desert him. Parliamentary Speaker Norbert Lammert spoke of his actions as "a nail in the coffin for confidence in democracy".
For the opposition Social Democrats, Wolfgang Thierse, vice-president of the lower house of parliament, the Bundestag, said Chancellor Merkel had been wrong to assume that what her defence minister had done as a private individual had no bearing on his position as minister.
By Tuesday the newspaper Die Welt reported that the number of academics who had signed the letter objecting to his continued role in the government had climbed to 51,500.
One of the most blistering comments came from law professor Oliver Lepsius, who succeeded his doctoral supervisor at Bayreuth.
"We have been taken by a fraud. His brazenness in deceiving honourable university personnel was unique," he wrote.