While a Harvard undergraduate, she was the Arts Editor of The Harvard Independent, and worked at Time magazine from 1973 to 1976. Subsequently, she spent nearly a decade as a senior staff reporter for The American Lawyer. In 1986, she was appointed as Editor in chief of Legal Times in Washington, D.C., serving for two years. From 1988 to 1997, she was a senior reporter in the Washington bureau of The Wall Street Journal, eventually rising to deputy bureau chief. She joined The New York Times in 1997, becoming its Washington bureau chief in December 2000.

Abramson was born in New York City and grew up in a Jewish home. She received her high school diploma from Ethical Culture Fieldston School and a BA in History and Literature from Harvard University and Radcliffe College in 1976.

In 1981, she married Harvard classmate Henry Little Griggs III. Griggs was then President of Triad, a political public relations company. He is self-described as a "writer, Editor and media-relations consultant specializing in nonprofit advocacy campaigns." They have two children.

In 1995, Abramson and her The Wall Street Journal colleague (and fellow Fieldston alumna) Jane Mayer co-authored Strange Justice: The Selling of Clarence Thomas, which detailed circumstances surrounding the confirmation hearings of Justice Clarence Thomas. Maureen Dowd would later write of having bonded with Abramson during that time. From 2000–01, she was a professor at Princeton University. She was elected a Fellow of the American Academy of Arts and Sciences in 2001.

Abramson was the Times' Washington Bureau chief during the turbulent period of Spring 2003 during the run-up to the war in Iraq and the Jayson Blair scandal, which led to the resignation of Executive Editor Howell Raines and Managing Editor Gerald Boyd. In a February 2013 interview, Abramson spoke of the conflict she had with Raines as D.C. bureau chief, saying, "Howell from the get-go just had no use for me. ... I did think about quitting." Abramson was named to the news managing Editor position (with co-Managing Editor John M. Geddes) by Raines' successor Bill Keller.

In May 2007, Abramson was seriously injured in a truck-pedestrian crash near the New York Times's headquarters in Times Square. She subsequently filed a lawsuit against the truck's driver, owner, and operator, who was involved in the crash, as well two companies involved in the crash.

In 2010, it was announced that Abramson was going to work on news content on the Times' website for six months.

On June 2, 2011, it was announced that Abramson would become the executive Editor of the Times in September 2011, replacing Bill Keller who would step down from the position to become a full-time Writer.

Abramson was scheduled to address the commencement exercises of Barnard College on May 14, 2012. Her speech was canceled after President Barack Obama requested to speak instead. She received an honorary degree at Fairleigh Dickinson's 69th Commencement Ceremony in May 2012.

In April 2013, Abramson was the subject of a sharply critical profile in Politico written by Dylan Byers entitled, "Turbulence at the Times," in which anonymous Times staffers called her "impossible" and "very, very unpopular." Abramson was deeply distressed by the report, later saying it made her cry.

On May 14, 2014, it was announced that Abramson had been fired from her position as executive Editor of the Times, and that Dean Baquet would succeed her in that role.

During the run-up to the 2016 U.S. presidential election, Abramson argued in a column for Guardian US that Hillary Clinton, whom she had covered as a reporter and Editor since the Whitewater controversy, was "fundamentally honest and trustworthy."

On February 19, 2018, Abramson followed up her 1995 book on Clarence Thomas and the Anita Hill hearings with a discussion concerning new evidence that Thomas had committed perjury which might be tied to possible impeachment. Abramson indicated that her reporting was initiated by an article by the Journalist Marcia Coyle from 2016 when Abramson stated, "Tipped to the post by a Maryland legal source who knew Smith (who made the allegations), Marcia Coyle, a highly regarded and scrupulously nonideological Supreme Court reporter for The National Law Journal, wrote a detailed story about (Moira) Smith’s allegation of butt-squeezing, which included corroboration from Smith’s roommates at the time of the dinner and from her former husband. Coyle’s story, which Thomas denied, was published October 27, 2016".