This study aimed to assess the feasibility and acceptability of implementing non-pharmaceutical interventions (NPIs) reserved for influenza pandemics (voluntary home quarantine, use of face masks by ill persons, childcare facility closures, school closures, and social distancing at schools, workplaces, and mass gatherings). Public health officials in all 50 states (including Washington, DC) and 8 territories, and a random sample of 822 local health departments (LHDs), were surveyed in 2019. The response rates for the states/ territories and LHDs were 75% (44/ 59) and 25% (206/ 822), respectively. Most of the state/ territorial respondents stated that the feasibility and acceptability of implementing NPIs were high, except for K-12 school closures lasting up to 6 weeks or 6 months. The LHD respondents also indicated that feasibility and acceptability were lowest for prolonged school closures. Compared to LHD respondents in suburban or urban areas, those in rural areas expressed lower feasibility and acceptability. Barriers to implementing NPIs included financial impact, compliance and difficulty in enforcement, perceived level of disease threat, and concerns regarding political implications. Proactive strategies to systematically address perceived barriers and promote disease prevention ahead of a new pandemic are needed to increase receptivity and consistent adoption of NPIs and other evidence-based countermeasures.