Stahl was born in Lynn, Massachusetts, of Jewish heritage, the daughter of Dorothy J. (née Tishler), and Louis E. Stahl, a food company executive. In 1977, Stahl married author Aaron Latham. They have once child : Taylor Stahl Latham. The couple currently lives in New York.

A graduate of Wheaton College, her career received a running start from her coverage of the Watergate affair. Stahl went on to become White House correspondent during the presidencies of Jimmy Carter, Ronald Reagan and George H. W. Bush. Stahl was the moderator of Face the Nation between September 1983 and May 1991. In addition, from 2002—2004, she hosted 48 Hours Investigates. In 2002, Stahl made headlines when Al Gore appeared on 60 Minutes and revealed for the first time that he would not run for president again in 2004. When Katie Couric was hired, CBS News asked Stahl to reduce her salary by $500,000 to accommodate Couric's salary, bringing her salary down to $1.8 million. In October 2007, Nicolas Sarkozy, President of France, stood up and walked away from an interview with Stahl, because she asked him about his relationship with his soon-to-be estranged spouse.

In 1998, she appeared in an episode of Frasier, playing herself in the episode "Desperately Seeking Closure".

She has written one book, Reporting Live, which was published in 1999.

She received a Doctorate of Humane Letters honoris causa from Colgate University in 2008 and a Doctorate of Humane Letters honoris causa from Loyola College in Maryland in 2008.

Lesley Stahl is one of the founding members, along with Liz Smith, Mary Wells Lawrence and Joni Evans of wowOwow.com, a website for women to talk about culture, politics, and gossip.

She is a member of the Council on Foreign Relations.