She attended the University of Virginia, graduating with highest distinction in 2002 with a Bachelor of Arts degree in foreign affairs and Middle Eastern studies and a minor in Arabic.

[7][8] Brennan began her business news career in 2002 at CNBC as a producer for prominent financial journalist Louis Rukeyser.

"At Bloomberg, she anchored InBusiness with Margaret Brennan, a weekday program broadcast live from the New York Stock Exchange that covered the top political, economic, and global financial news impacting the marketplace.

Brennan covered top breaking news stories involving the European debt crisis, the largest insider trading case in U.S. history, and the BP oil spill.

Brennan was also part of the CBS News team honored with a 2012-2013 Alfred I. Dupont-Columbia Award for coverage of the Newtown tragedy.

At a press conference on September 9, 2013, she asked Secretary of State John Kerry about any possibility for the Syrian government to avoid a U.S. strike.

Kerry's answer, that Assad could "turn over every single bit of his chemical weapons to the international community in the next week"[22] (although later his answer was retracted as "a rhetorical argument about the impossibility and unlikelihood of Assad turning over chemical weapons he has denied using" by a State Department spokesperson), led Russia's foreign minister Sergey V. Lavrov to propose this as a solution to the crisis.

Brennan won an Emmy Award for "Outstanding News Special" for her coverage of the Parkland High School shooting.

On April 11, 2015, Brennan married Yado Yakub, a Syrian-American[30] attorney who is a judge advocate in the United States Marine Corps.

[31][32][33] During an appearance on The Late Show with Stephen Colbert on April 30, 2018, Brennan announced she was pregnant with their first child, a boy who was born on September 11, 2018.