"Today I am announcing my resignation from Congress," Weiner said amid jeers and cheers.
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Weiner, 46, apologized for his "personal mistakes," and thanked his wife Huma Abedin for standing by him "through this entire period."
"I make this apology to my neighbors and my constituents but I make it particularly to my wife, Huma," he said.
Abedin, a top aide to Secretary of State Hilary Clinton, returned Wednesday from a work trip through the Middle East and Africa with Clinton.
According to colleagues, Weiner had said he preferred to wait for his wife's return before making any decisions pertaining to his career.
Abedin is pregnant with the couple's first child.
On Monday, the House agreed to Weiner's request for a two-week leave of absence. Weiner said he was seeking treatment for unhealthy sexual urges and sexual addiction. He said he hoped to be a better husband and a healthier person.
Political experts say leaves of absence are routine in the house.
Weiner will continue to receive his pay and benefits.
The news came after new lewd photos of the congressman emerged.
TMZ published photos of Weiner, in various states of undress, which he apparently took of himself in a locker room.
TMZ reported that they were taken in the House members' gym and sent to at least one woman.
Weiner's office had no immediate comment.
Weiner admitted to exchanging "messages and photos of explicit nature with about six women in the last three years," communicating with them online and, occasionally, on the phone.
Weiner said that he has "made some serious mistakes" and is trying to redeem himself, adding that his wife, Huma Abedin, a senior aide to Secretary of State Hillary Clinton is doing well.
Reports have surfaced revealing that Weiner had engaged in online contact with a 17-year-old girl.
Weiner's office said that there had been no inappropriate communication between the two. Delaware police are investigating the claim.
House Minority Leader Nancy Pelosi and other top Democrats had called for Weiner's resignation.
Rep. Debbie Wasserman Schultz (D-Fla.) called Weiner's behavior "indefensible."