Petraeus' resignation shocked Washington's intelligence and political communities. It was a sudden end to the public career of the best-known general of the post 9/11 wars, a man credited with salvaging the US conflict in Iraq and sometimes mentioned as a potential Republican presidential candidate. His service was effusively praised on Friday in statements from both Republican and Democratic lawmakers.
Petraeus, who turned 60 on Wednesday, told CIA employees in a statement that he had met with President Barack Obama at the White House on Thursday and asked to be allowed to resign. On Friday, the president accepted.
Petraeus told his staffers he was guilty of "extremely poor judgment" in the affair. "Such behavior is unacceptable, both as a husband and as the leader of an organization such as ours."
He has been married for 38 years to Holly Petraeus, whom he met when he was a cadet at the US Military Academy at West Point, New York. She was the daughter of the academy superintendent. They have two children, and their son led an infantry platoon in Afghanistan.
Obama said in a statement that the retired general had provided "extraordinary service to the United States for decades" and had given a lifetime of service that "made our country safer and stronger." Obama called him "one of the outstanding general officers of his generation."
The president said that CIA deputy director Michael Morell would serve as acting director. Morell was the key CIA aide in the White House to President George W Bush during the Sept 11, 2001, terror attacks.
"I am completely confident that the CIA will continue to thrive and carry out its essential mission," Obama said.
The resignation comes at a sensitive time. The administration and the CIA have struggled to defend security and intelligence lapses before the attack that killed the US ambassador to Libya and three others. It was an issue during the presidential campaign that ended with Obama's re-election on Tuesday.
The CIA has come under intense scrutiny for providing the White House and other administration officials with talking points that led them to say the Benghazi attack was a result of a film protest, not a militant terror attack. It has become clear that the CIA was aware the attack was distinct from the film protests roiling across other parts of the Muslim world.
Morell rather than Petraeus now is expected to testify at closed congressional briefings next week on the Sept 11 attacks on the consulate in Benghazi.
For the director of the CIA, being engaged in an extramarital affair is considered a serious breach of security and a counterintelligence threat. If a foreign government had learned of the affair, the reasoning goes, Petraeus or the person with whom he was involved could have been blackmailed or otherwise compromised. Military justice considers conduct such as an extramarital affair to be possible grounds for court martial.
Failure to resign also could create the perception for the rank-and-file that such behavior is acceptable.
At FBI headquarters, spokesman Paul Bresson declined to comment on the information that the affair had been discovered in the course of an investigation by the bureau.
Holly Petraeus is known for her work helping military families. She joined the new Consumer Financial Protection Bureau to set up an office dedicated to helping service members with financial issues.
Though Obama made no direct mention of Petraeus' reason for resigning, he offered his thoughts and prayers to the general and his wife, saying that Holly Petraeus had "done so much to help military families through her own work. I wish them the very best at this difficult time."
Petraeus, who became CIA director in September 2011, was known as a shrewd thinker and hard-charging competitor. His management style was recently lauded in a Newsweek article by Paula Broadwell, co-author of the biography, "All In: The Education of General David Petraeus."
The article listed Petraeus' "rules for living." No. 5 was: "We all make mistakes. The key is to recognize them, to learn from them, and to take off the rear view mirrors — drive on and avoid making them again."
Petraeus told his CIA employees that he treasured his work with them "and I will always regret the circumstances that brought that work with you to an end."
The director of national intelligence, James Clapper, said Petraeus' departure represented "the loss of one of our nation's most respected public servants. From his long, illustrious Army career to his leadership at the helm of CIA, Dave has redefined what it means to serve and sacrifice for one's country."
Other CIA directors have resigned under unflattering circumstances.
CIA director Jim Woolsey left over the discovery of a KGB mole and director John Deutch left after the revelation that he had kept classified information on his home computer.
Bush sent Petraeus to Iraq in February 2007, at the peak of sectarian violence, to turn things around as head of U.S. forces. He oversaw an influx of 30,000 US troops and moved troops out of big bases so they could work more closely with Iraqi forces scattered throughout Baghdad.
Petraeus' success was credited with paving the way for the eventual US withdrawal.
"His inspirational leadership and his genius were directly responsible - after years of failure - for the success of the surge in Iraq," said Sen. John McCain, the Republican who ran unsuccessfully for president against Obama in 2008.
After Iraq, Bush made Petraeus commander of US Central Command, overseeing all US military operations in the greater Middle East, including Afghanistan and Pakistan.
When the top US commander in Afghanistan, Gen. Stanley McChrystal, was relieved of duty in June 2010 for comments in a magazine story, Obama asked Petraeus to take over in Kabul and the general quickly agreed.
In the months that followed, Petraeus helped lead the push to add more US troops to that war and dramatically boost the effort to train Afghan soldiers and police.
House Homeland Security Chairman Peter King, a Republican, said he regretted Petraeus' resignation, calling him "one of America's most outstanding and distinguished military leaders and a true American patriot."
Senate Intelligence Committee Chairman Dianne Feinstein also regretted the resignation but gave Morell high marks, too.
Morell had served as deputy director since May 2010, after holding a number of top roles, including director for the agency's analytical arm, which helps feed intelligence into the president's daily brief. He also worked as an aide to former CIA director George Tenet.
"I wish President Obama had not accepted this resignation," Feinstein said of Petraeus, "but I understand and respect the decision."