"I'm announcing my resignation from Congress so my colleagues can get back to work, my neighbors can choose a new representative and, most importantly, that my wife and I can continue to heal from the damage I have caused," Weiner said at a news conference made raucous by loud yells from hecklers.
"I had hoped to be able to continue the work that the citizens of my district elected me to do," he said. "Unfortunately, the distraction that I have created has made that impossible."
Weiner, 46, made the announcement at a senior center in Brooklyn, New York, where he first launched his political career nearly two decades ago. He said that despite his indiscretions, he would continue to pursue the spirit of public service that first led him to run for office.
"I'll be looking for other ways to contribute my talents to make sure that we live up to that most New York and American of ideals," he said just before concluding his remarks.
He did not take reporters' questions. His wife was not present.
Weiner's decision to leave office came 10 days after his news conference admitting he lied to his family, colleagues and constituents about risque online behavior with multiple women while married to Abedin.
While polls showed a majority of Weiner's constituents did not think he should resign, the embattled congressman had come under enormous pressure from Democratic Party leaders to step down because the swirling scandal was seen as a "distraction."
"Today, he made the right judgment in resigning," Pelosi said in a statement. "I pray for him and his family and wish them well."
Pelosi signaled at an earlier news conference that Democrats now intend to pivot back to talking about the issues they'd rather discuss, including slamming Republicans on the budget and Medicare overhaul. Attention also shifts to who will replace Weiner.
When New York Gov. Andrew Cuomo officially announces the congressional vacancy, the state must hold a special election within 70 to 80 days, according to state law. The election, which will likely occur in early fall, will be the third in New York in less than one year triggered by the resignation of a congressman because of a sex scandal.
Weiner Broke News During Picnic
Weiner called House leaders Wednesday night at a White House picnic to inform them he would resign today, sources told ABC News.
A Democratic source said Pelosi of California and Rep. Steve Israel of New York, chairman of the Democratic Congressional Campaign Committee, stepped away from the picnic to take a phone call from Weiner, when he told them of his decision.
News of Weiner's decision broke early today as Democrats prepared to consider whether to strip the congressman of his committee assignments in an effort to limit his influence and push him out.
"Our caucus understands our concern for the rights of the individual member," Pelosi said after a meeting Tuesday with House Democrats, "but also our higher responsibility to our country to uphold a high ethical standard in the Congress of the United States."
Weiner, who has not been charged with or convicted of violating any laws or House ethics rules, had insisted he would remain in office despite the pressure from his colleagues. On Monday, he received a two-week temporary leave of absence from the House to receive "treatment" for an undisclosed condition at an unknown location.
Meanwhile, Weiner's wife returned from an overseas trip with Secretary of State Hillary Clinton early Wednesday morning and met with her husband in person for the first time since the sexting scandal broke. Weiner had told friends he was waiting for her return before making any decision about his political future.
ABC News' Amy Walter, Chris Vlasto, John Parkinson and Marisa Bramwell contributed to this report.