Walter Isaacson was born in New Orleans, Louisiana. After graduating from New Orleans' Isidore Newman School and a summer at Deep Springs College as a participant in the Telluride Association Summer Program (TASP), Isaacson attended Harvard College (A.B. in history and literature) and University of Oxford, where he was a Rhodes Scholar at Pembroke College (M.A. in Philosophy, Politics, and Economics).

Walter Isaacson began his career in journalism at The Sunday Times of London and then the New Orleans Times-Picayune/States-Item. He joined TIME in 1978 and served as a political correspondent, national editor, and editor of new media before becoming the magazine's fourteenth managing editor in 1996. He became Chairman and CEO of CNN in 2001, and then president and CEO of the Aspen Institute in 2003.

He is the author of American Sketches (2009), Einstein: His Life and Universe (2007), Benjamin Franklin: An American Life (2003) and of Kissinger: A Biography (1992), and is the co-author, with Evan Thomas, of The Wise Men: Six Friends and the World They Made (1986). He is the editor of Profiles in Leadership: Historians on the Elusive Quality of Greatness (2010 W.W. Norton).

He is the chairman of the board of Teach for America and of the Broadcasting Board of Governors. He is on the Board of United Airlines, Tulane University, Overseers of Harvard University, and the Bloomberg Family Foundation.

In October 2005, Louisiana Governor Kathleen Blanco appointed Isaacson vice chairman of the Louisiana Recovery Authority, a thirty-three-member policymaking board, led by Norman C. Francis, the president of Xavier University. In December 2007, he was appointed by President George W. Bush to the chairman of the U.S.-Palestinian Public-Private Partnership, which seeks to create economic and educational opportunities in the Palestinian territories. He also serves as the cochair of the U.S.-Vietnamese Dialogue on Agent Orange, which in January 2008 announced completion of a project to contain the dioxin left behind by the U.S. at the Da Nang air base and plans to build health centers and a dioxin laboratory in the affected regions.

The New York Times has reported that he is working on a biography of Steve Jobs that is said to have the Apple CEO's full cooperation.

On September 29, 2010 Isaacson gave a speech in Washington D.C. at a Broadcasting Board of Governors dinner marking the 60th anniversary of Radio Free Europe. Isaacson said, "We can't let ourselves be out-communicated by our enemies" and cited a report from the partially U.S. taxpayer-funded NGO to support his claim that "autocratic leaders are investing billions of dollars in media resources to influence global opinion. You've got Russia Today, Iran's Press TV, Venezuela's Telesur, and of course, China is launching an international broadcasting 24 hour news channel with correspondents around the world...spends...partly set aside 6 to 10 billion dollars...we've gotta go to Capitol Hill with that number." When asked by RT America to elaborate on his "enemies" remark in a telephone interview, Isaacson said, "I do not think of Russia or RT as an enemy, and certainly did not mean to imply that they're an enemy, so that's just not right." According to Russia Today, the budgets of RT, Telesur and Press TV combined do not match the BBG's Congressional-funded annual $757 million operating budget. Isaacson's remarks were also clarified by a BBG press release affirming that his 'enemies' remarks were about America's terror-plotting adversaries in Afghanistan, not Russia and China.

When asked to comment on the controversy, Josh Rogin, a staff writer for magazine said, "They [the BBG] have two conflicting missions. One is to report the news objectively and the other is to be a tool of American foreign policy'. He said that overall, the conflict does not speak well for the 'objectivity and credibility' of the news organizations."