The notable New York author Washington Irving was a close friend of Astor for decades and had helped the philanthropist design the Astor Library. Irving served as President of the library's Board of Trustees from 1848 until his death in 1859, shaping the library's collecting policies with his strong sensibility regarding European intellectual life. Subsequently, the library hired nationally prominent experts to guide its collections policies; they reported directly to directors John Shaw Billings (who also developed the National Library of Medicine), Edwin H. Anderson, Harry Miller Lydenberg, Franklin F. Hopper, Ralph A. Beals, and Edward Freehafer (1954-70). They emphasized expertise, objectivity, and a very broad worldwide range of knowledge in acquiring, preserving, organizing, and making available to the general population nearly 12 million books and 26.5 million additional items. The directors in turn reported to an elite board of trustees, chiefly elderly, well-educated, philanthropic, predominantly Protestant, upper-class white men with commanding positions in American society. They saw their role as protecting the library's autonomy from politicians as well as bestowing upon it status, resources, and prudent care.  Representative of many major board decisions was the purchase in 1931 of the private library of Grand Duke Vladimir Alexandrovich (1847-1909), uncle of the last tsar. This was one of the largest acquisitions of Russian books and photographic materials; at the time, the Soviet government had a policy of selling its cultural collections abroad for gold.  The military drew extensively from the library's map and book collections in the world wars, including hiring its staff. For example, the Map Division's chief Walter Ristow was appointed as head of the geography section of the War Department's New York Office of Military Intelligence from 1942 to 1945. Ristow and his staff discovered, copied, and loaned thousands of strategic, rare or unique maps to war agencies in need of information not available through other sources.

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