Boies began her legal career in 1975 when she won the annual fellowship to the staff of the United States Senate Committee on Commerce, Science, and Transportation.

In 1977, she transferred to the White House Office and served as assistant director of the domestic policy staff with a portfolio of economic deregulation relating to the airline, trucking, and rail industries.

She departed CBS upon the birth of her second child in 1985 and opened a private law practice in New York that became Boies & McInnis LLP.

Boies served two terms as a member of the board of directors of the Council on Foreign Relations 2010–2020[5] and chaired its Committee on Nominations and Governance.

[7] She served on the board of the MIT Center for International Studies and the Executive Committee[8] and the Dean's Council of the Harvard Kennedy School.

[13] She served a term on the committee established by President Dwight D. Eisenhower to conduct nonpartisan peer reviews of federal judicial nominees including to the Supreme Court of the United States.

[35] The Mary and David Boies Fellowship provide assistance to students from Afghanistan, Iraq, Israel, Palestine, and the former Soviet Union countries in Central Asia.

There is a "Mary and David Boies Reading Room" at the Villa Grebovka, headquarters of the Central European and Eurasian Law Institute in Prague, Czech Republic.

[39] For many years the Boies gave an annual picnic at their home for the incoming Teach for America corps for New York City (300–500 people).