Weiner delivered a 5-minute statement at the same Brooklyn senior center where he announced his bid for a New York City Council seat 20 years ago.
"I am here today to again apologize for the personal mistakes I have made and the embarrassment I have caused. I make this apology to my neighbors and my constituents, but I make it particularly to my wife, Huma," Weiner said.
"I had hoped to be able to continue the work that the citizens of my district elected me to do: to fight for the middle class and those struggling to make it.
"Unfortunately, the distraction that I have created has made that impossible. So today I am 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 earlier told friends he reached his decision after discussing the matter with his wife, U.S. State Department aide Huma Abedin, after she returned home from a trip abroad with her boss, Secretary of State Hillary Clinton, a source told The New York Times. The couple were married 11 months ago, and Abedin is reportedly pregnant with their first child.
Weiner called House Minority Leader Nancy Pelosi of California and Democratic Congressional Campaign Committee Chairman Steve Israel of New York Wednesday notifying them of his intention to resign, MSNBC reported.
The news comes as Democratic leaders were to meet Thursday to discuss whether to strip Weiner of his committee assignments.
A sometimes emotional Weiner last week admitted he lied about inappropriate communications, including sending lewd photos to women he met through online social media.
The House Monday approved a two-week leave of absence for Weiner while he seeks professional treatment.
Pressure on Weiner to leave the House had been building for days. Earlier this week, President Obama said he would step down if he were in Weiner's shoes.
The House Ethics Committee had opened an inquiry into Weiner's conduct, raising the prospect that he could be formally charged and sanctioned. A decision to resign likely would end the investigation, since the committee has jurisdiction only over the actions of congressional members.