Many adults in the United States do not reach the recommended levels of activity needed for health benefits. Single-female caregivers present a unique and vulnerable population that is often less active than their partnered peers or single-male caregivers. The primary objective of this cross-sectional investigation was to identify the prevalence of physical inactivity in single-family, female-led households and determine differences in personal factors and social characteristics between physically active and not physically active single-female caregivers. A secondary objective was to examine associations among the social characteristic variables and physical inactivity in single-female caregiver households. Finally, we examined the odds single-female caregivers who are physically inactive reported chronic health conditions. Cross-sectional survey design. We used the 2020 Behavioral Risk Factor Surveillance System (BRFSS) data. Participants were selected based on pre-determined criteria for inclusion. There was a 39.3% prevalence of physical inactivity among single-female caregivers in the sample. Single-female caregivers who were physically inactive had greater odds of having a history of multiple chronic health conditions. Healthcare providers and other community stakeholders should explore existing physical activity promotion strategies to increase physical activity in single-female caregivers. Future research should employ more rigorous, prospective research designs to determine if these chronic conditions and various social characteristics are caused by physical inactivity.