Weiner took the Specialized High Schools Admissions Test, an examination used to determine admission to all but one of New York City's specialized high schools, and was admitted to Brooklyn Technical High School, from which he graduated in 1981. He attended the State University of New York at Plattsburgh, and spent his junior year as an exchange student at the College of william & Mary, where he was friends with Future comic and political commentator Jon Stewart. Stewart acknowledged the friendship when he poked fun at him during the sexting scandal in 2011. His interests turned towards politics; he became active in student government and was named most effective student senator.

After he received his Bachelor of Arts degree in political science in 1985, Weiner joined the staff of then-United States Representative and current Senator Charles Schumer. He worked in Schumer's Washington, D.C. office for three years, then transferred to the district office in Brooklyn in 1988, when Schumer encouraged him to become involved in local politics.

After working for Schumer for six years, Weiner got his first chance at political office in 1991 when the New York City Council was expanded from 35 to 51 seats. Weiner was considered a long-shot because he faced strong competition in the Democratic primary elections from two other candidates who had better local name recognition and funding. Weiner narrowly won the primary, besting Adele Cohen by less than 200 votes. Controversy ensued in the last weeks of the campaign after Weiner's campaign anonymously spread leaflets around the district that had alleged ties between Cohen and the so-called "Jackson-Dinkins agenda"; the leaflets referred to the Crown Heights riots earlier in the year, after which white residents had seen Jesse Jackson, who became notorious for his earlier remarks about New York City as "Hymietown", and then-mayor David Dinkins as having been beholden to the predominantly African-American rioters and therefore endangering whites.

In 1998, Weiner ran for Congress from New York's 9th congressional district, which was the seat held by his mentor, Chuck Schumer, who was running for the U.S. Senate. Weiner won the Democratic primary election, which was tantamount to election in the heavily Democratic district that included parts of southern Brooklyn and south and central Queens.

Weiner was born in the New York City borough of Brooklyn, the middle son of his Jewish parents, Mort Weiner, a Lawyer, and his wife Frances (née Finkelstein), a public high school math Teacher. The family lived for a time in the Park Slope neighborhood of Brooklyn. His older brother Seth was 39 years old when he was killed by a hit-and-run driver in 2000. His younger brother, Jason, is a chef and co-owner of several New York restaurants.

In 2002, Weiner voted to give President Bush the power to use military force against Iraq. In May 2006, Weiner attempted to bar the Palestinian delegation from entering the United Nations. He added that the delegation "should start packing their little Palestinian terrorist bags", and went on to claim that Human Rights Watch, The New York Times, and Amnesty International are all biased against Israel.

Weiner received a 100% rating from the NARAL Pro-Choice America in 2003 and a 0% rating from National Right to Life Committee 2006, which indicated a strong pro-choice voting record. He was critical of the 2009 Stupak-Pitts Amendment to the health reform bill, calling it "unnecessary and divisive" and saying it would prevent health insurers from offering abortion coverage regardless of whether an individual uses federal funds to purchase an insurance plan.

Weiner sought the Democratic nomination to run for New York City mayor in 2005, vying against three other candidates. He had a three-part pitch to voters that included criticizing sitting Mayor Michael Bloomberg for his top-down style of management and promising a more democratic approach; against "passivity in City Hall" and for getting more federal money for the city; and a series of ideas on how to get the city to work better. He presented a book of 50 "Real Solutions" and among his policy proposals were fixes for the health care and educational systems. One idea already in play was a neighborhood scrubbing-up program he dubbed "Weiner's Cleaners".

On July 29, 2007, Weiner and Rep. Jerrold Nadler (D-N.Y.) objected to a $20-billion arms deal that the Bush Administration had negotiated with Saudi Arabia because they didn't want to provide "sophisticated weapons to a country that they believe has not done enough to stop terrorism", noting that 15 of the 19 hijackers of September 11, 2001, were Saudis. Weiner made the announcement outside of the Saudi Arabian consulate in Washington, stating, "We need to send a crystal clear message to the Saudi Arabian government that their tacit approval of terrorism can't go unpunished." The two intended to use a provision of the Arms Export Control Act to review the deal and pass a Joint Resolution of Disapproval.

In July 2008, The New York Times characterized Weiner as one of the most intense and demanding of bosses. The newspaper described him as a person who often worked long hours with his staff and required them to be in constant contact via BlackBerry. He frequently yelled at them and occasionally threw office furniture in anger. As a result of Weiner's actions, the Times reported that he had one of the highest staff turnover rates of any member of Congress; this included the departure of three chiefs of staff within an 18-month period. Weiner admitted he pushed his aides hard but said that his speaking at a high decibel level was part of his background and style, not necessarily shouting. Though some former employees were critical of his supervisory practices, others praised him for his intense involvement in constituent concerns and readiness to fight for New York City.

In May 2009, he became engaged to Huma Abedin, a long-time personal aide to Hillary Clinton, and they married in July 2010, with former President Bill Clinton officiating. Abedin is a practicing Muslim of Indian and Pakistani descent. In December 2011, Abedin gave birth to a son, Jordan Zain Weiner.

In response to pressure from Weiner, YouTube removed some of Anwar al-Awlaki's inflammatory videos from its website in November 2010. Weiner voted against the Tax Relief, Unemployment Insurance Reauthorization, and Job Creation Act of 2010. As a prominent Democratic opponent of the tax cut package passed by Congress, Weiner said Republicans had gotten the better of President Obama in the negotiations to reach an agreement on the $858 billion deal and said the Republicans turned out to be "better poker players" than Obama.

In July 2011 (which was less than a month after he left Congress), Weiner created the consulting firm Woolf-Weiner Associates. He advised over a dozen companies that included electronic medical records providers and biofuel firms. He worked with Covington & Burling, an international law firm. According to 2012 public disclosures, his work helped increase his combined family income to $496,000. Weiner argued that despite contacting members of Congress on behalf of his clients, his work did not meet the legal definition of lobbying. This was based on the so-called "Daschle Loophole" in the Lobbying Disclosure Act, which requires only those who spend more than 20% of their time lobbying to register as lobbyists.

In 2013, a production called The Weiner Monologues premiered at the Access Theater. Directed by Jonathan Harper Schlieman, the show was based on media coverage of Weiner's sexting scandal. In 2014, he had a cameo appearance in an Alpha House episode.

By September 2015, his employment at MWW had ended, with the firm's head Michael Kempner stating "It has become clear that a handful of people and a few media outlets continue to be fixated on Anthony". According to Politico New York, Weiner reportedly first learned of Kempner's decision through a mass email.

On August 29, 2016, the New York Daily News said it would no longer carry Weiner's columns, which included his writings on New York City politics. On the same day, television channel NY1 said Weiner would not be reprising his contributor role on any of its shows.

In August 2016, Abedin announced that she was separating from Weiner. In early 2017, Abedin announced her intent to file for divorce with sole physical custody of their son. On May 19, 2017, after he pleaded guilty, she filed for divorce. The next month, the FBI and the NYPD announced their investigation into newly published communications between Weiner and a 15-year-old girl in North Carolina, who alleged in an interview with The Daily Mail that she and Weiner had exchanged messages for several months beginning in January 2016. Huma Abedin and Anthony Weiner withdrew their divorce case from court in January 2018, claiming they did so in order to spare their six year-old son further embarrassment.