The United States has engaged with Indigenous nations on a government-to-government basis via federal treaties representing substantial international commitments since the origins of the republic. The first treaties sent to the Senate for ratification under the Constitution of 1789 were treaties with Indigenous nations. Treaties with Indigenous nations provided the means by which approximately one billion acres of land entered the national domain of the United States prior to 1900, at an average price of seventy-five cents per acre – the United States confiscated or claimed another billion acres of Indigenous land without compensation. Despite subsequent efforts of American federal authorities to alter these arrangements, the weight of evidence indicates that the relationship remains primarily one of a nation-to-nation association. Integration of the history of federal relations with Indigenous nations with American foreign relations history sheds important new light on the fundamental linkages between these seemingly distinct state practices from the beginnings of the American republic.