The United States of America was created around the concept of federalism, which embraces the principles of shared governance and balance of power between the sovereign states and the supreme national government. Due to distinctive constitutional, legal, organizational, and historical reasons, the U.S. National Guard operates as a dual-purpose force within this system of federal government. As a result, the Guard has separate state and federal missions and separate and independent command and control authorities. This study is exploratory in nature and its primary purpose is to understand how federalism affects the National Guard’s domestic emergency response mission and to relate the findings to practice. The study follows a mixed methods concurrent nested strategy with a qualitative predominance. Qualitative data was collected through personal interviews, observation, and documented literature. Quantitative data was collected through an online survey administered to the fifty-four offices of the adjutant generals. The data was simultaneously analyzed to answer the primary research question and four related secondary questions. Variables were identified and a framework was created. The findings indicate that increasingly strong federal influences have affected nearly every aspect of the National Guard’s existence. The two independent variables of state government influences and federal government influence affect the dependent variable, the National Guard’s emergency response mission, through a series of moderator variables: mission and funding, organization and structure, personnel and equipment, and planning and training. Additionally, related secondary research questions on the topics of emergency management assistance compacts, organizational and structural alternatives, command and control structures, and State Defense Forces were examined. This exploratory study lays the foundation for future research.