Mitchell graduated with a B.A. in English literature from the University of Pennsylvania in 1967, where she served as News Director of student radio station WXPN. She joined Philadelphia then-NBC affiliate KYW radio and KYW-TV as a reporter that same year.

After several years at KYW, she moved to CBS affiliate WTOP in Washington, D.C., in 1976. Two years later, Mitchell moved to NBC's network news operation, where she served as a general correspondent. In 1979, she was named the NBC News Energy correspondent and reported on the late 1970s energy crisis and the Three Mile Island nuclear accident. Mitchell also covered the White House from 1981 until becoming Chief Congressional Correspondent in 1988.

She has been the Chief Foreign Affairs Correspondent for NBC News since November 1994. Previously, she had served as Chief White House Correspondent (1993–1994) and Chief Congressional Correspondent (1988–1992) for NBC News.

In 2005, Mitchell published a book entitled Talking Back... to Presidents, Dictators, and Assorted Scoundrels (ISBN 0143038737), chronicling her work as a journalist.

Mitchell hosts a news program on MSNBC entitled Andrea Mitchell Reports. It broadcasts weekdays from 1 PM ET/10 AM PT.

Role in the Plame Affair

A report in The Washington Post ("Bush Administration Is Focus of Inquiry CIA Agent's Identity Was Leaked to Media" by Mike Allen and Dana Priest, Washington Post, September 28, 2003), that Mitchell was an original recipient of the leak of Valerie Plame's identity led to her being questioned by the Federal Bureau of Investigation in the case. While Mitchell never appeared before the grand jury in the indictment or in the trial of I. Lewis Libby, she was on the subpoena list as a person of interest. In October 2003, on the Capitol Report, Mitchell made a statement which Libby's defense construed to mean that it was widely known among journalists that Joe Wilson's wife was in the Central Intelligence Agency (CIA), a statement that she later recanted.

MURRAY: And the second question is: Do we have any idea how widely known it was in Washington that Joe Wilson's wife worked for the CIA?MITCHELL: It was widely known amongst those of us who cover the intelligence community and who were actively engaged in trying to track down who among the foreign service community was the envoy to Niger. But frankly I wasn't aware of her actual role at the CIA and the fact that she had a covert role involving weapons of mass destruction, not until Bob Novak wrote it.

As a reporter, Mitchell has covered the case without acknowledging her own involvement. As a guest on Don Imus's radio program, Mitchell answered a number of his questions about the case and her involvement. She jokingly called the sharp-tongued radio personality her "personal terrorist".

Sudan incident

During a news conference in Khartoum in July, 2005, Mitchell was forcibly ejected from a room after asking Sudanese President Omar el-Bashir some pointed questions. They included: "Can you tell us why the violence is continuing?" (referring to genocide in Sudan's Darfur province) and "Can you tell us why the government is supporting the militias?" "Why should Americans believe your promises?" At this point two armed security guards grabbed her and forcibly shoved her out of the room.

After the incident Mitchell said: "It is our job to ask. They can always say 'no comment' but to drag a reporter out just for asking is inexcusable behavior."

Prior to the incident, Sudanese officials expressed reservations about allowing American newspaper or television reporters to join the Sudanese press pool. Sean McCormack, the U.S. State Department's assistant secretary for public affairs, said to his Sudanese counterpart, "I'll convey your desires about not permitting reporters to ask questions, but that's all I'll do. We have a free press." McCormack's Sudanese counterpart replied, "There is no freedom of the press here."

McCain's "cone of silence"

Following a forum at the Saddleback Church in August 2008 on values and ethics conducted by Christian pastor and author Rick Warren between the presidential candidates Barack Obama and John McCain, Mitchell reported that the Obama campaign accused McCain of overhearing the questions asked of Obama, when McCain was supposed to be in a secluded "cone of silence."

According to the New York Times, Warren assured the audience that “we have safely placed Senator McCain in a cone of silence” and that he could not hear the questions. However, McCain was not in the building at the time; he was still in transit, without supervision by the forum staff. Despite Assurances, McCain Wasn’t in a ‘Cone of Silence’, August 17, 2008, New York Times. According to CNN, Warren said "we flat out asked him" if he heard any of the questions. The McCain campaign asserted "that McCain did not hear or see any of the broadcast" in the motorcade or after he arrived. The accusation provoked the McCain campaign into writing a letter to NBC News, complaining of biased news coverage. The dispute expanded, including reports on other networks such as CBS noting that there were allegations McCain had access to "communications devices" which may have advised him of the questions even if he was not listening directly to the broadcast itself. McCain's "Cone Of Silence" At Saddleback, August 18, 2008, CBS News.

Controversy during Obama Campaign

During an appearance on MSNBC on June 5, 2008, Mitchell came under fire when she referred to the voters of the southwest Virginia region as rednecks. On June 9, Mitchell apologized for her comment stating:

And now, a point of personal privilege. I owe an apology to the good people of , for something stupid that I said last week. I was trying to explain, based on reporting from Democratic strategists, why Barack Obama was campaigning in southwest Virginia, but without attribution or explanation, I used a term strategists often use to demean an entire community. No excuses, I'm really sorry. As they say, when I make a mistake, it's a beaut.

Mitchell was born in New York City, New York She married her second husband, former Federal Reserve Chairman Alan Greenspan, in 1997. Previously, she was married to Gil Jackson; that marriage ended in divorce in the mid-1970s.