The design of the room includes many nautical motifs - such as shells over the Italian and French marble panels; seahorses and dolphins in the cast iron railing at the second floor balcony; stars for navigation in the ceiling and the compass in the center of the floor. The floor is the original English Minton tile floor. The room contains the only surviving original lighting fixtures in the building.

The Navy Department vacated the building between 1918 and 1921, and by 1930 the building was renamed the Department of State Building (although the War Department did not completely move out until 1938); by 1949 the building was renamed the Executive Office Building. The Treaty Room was used for presidential press conferences from 1955 until 1961. Eisenhower held the first televised presidential press conference here in January 1955.

The name "Indian Treaty Room" came about sometime during the 1930s, and it is still not clear as to where it originated, despite extensive research. Some say it is due to the fact that during the 1930s the War Department stored papers there, including treaties with the American Indian nations.

Although most treaties were signed in the State Department Diplomatic Reception Room (212-214) and the Secretary of State's office (208), a few were signed in the Indian Treaty Room. These include Bretton Woods - establishing the International Monetary Fund (IMF), Peace Treaties with Rumania, Italy and Hungary after WWII, and the UN Charter.

Restoration of the main room was done between 1984 and 1985 (the upper north alcove was opened in 1991). Today the room is used for meetings and receptions.