Her parents are Harvey M. Applebaum, a Covington and Burling partner, and Elizabeth Applebaum of the Corcoran Gallery of Art. She graduated from the Sidwell Friends School (1982). She earned a B.A. (summa cum laude) at Yale University (1986), where she was elected to Phi Beta Kappa. As a Marshall Scholar at the London School of Economics she earned a master's degree in international relations (1987). She studied at St Antony's College, Oxford before moving to Warsaw, Poland in 1988 as a correspondent for The Economist.

She was an editor at The Spectator, and a columnist for both the Daily Telegraph and Sunday Telegraph. She also wrote for The Independent. Working for The Economist, she provided coverage of important social and political transitions in Eastern Europe, both before and after the Fall of the Berlin Wall in 1989. In 1992 she was awarded the Charles Douglas-Home Memorial Trust Award.

Applebaum lived in London and Warsaw during the 1990s, and was for several years a widely read columnist for London's Evening Standard newspaper. She wrote about the workings of Westminster, and opined on issues foreign and domestic.

Applebaum's first book, Between East and West, is a travelogue, and was awarded an Adolph Bentinck Prize in 1996. Her second book, A History, was published in 2003 and was awarded the 2004 Pulitzer Prize for General Non-Fiction writing.

Applebaum is fluent in English, French, Polish and Russian.

On May 24, 2006, she wrote that she was leaving Washington to live again in Poland.

Applebaum was a George Herbert Walker Bush/Axel Springer Fellow at the American Academy in Berlin, Germany, in spring 2008. Applebaum was also an adjunct fellow at the American Enterprise Institute think tank.

In a short blog posting in September 2009, Applebaum condemned the 2009 arrest of Roman Polanski. Critics claimed that she minimized Polanski's crimes and did not disclose that her husband was seeking his release. She responded in a second blog post that she had previously disclosed her husband's job, was not a spokesman for him, and "had no idea that the Polish government would or could lobby for Polanski's release".

Applebaum married Polish Foreign Minister Rados?aw Sikorski in 1992. They have two sons: Alexander and Tadeusz.