Physical inactivity (PI) has been described as an independent risk factor for a large number of major non-communicable diseases and is associated with an increased risk of premature death. Additionally, sedentary behaviour has been associated with increased overall mortality. Additionally, sedentary behaviour has been associated with increased overall mortality. We estimated the national prevalence of PI and sedentary behaviour using the Global Physical Activity Questionnaire version 2. Using unconditional logistic regressions, the possible risk factors for PI were assessed. Overhalf of the people included in this study (54.9%; 95% CI: 54.1–57.3%) were physically inactive, with the median time spent engaged in sedentary behaviour being 120 min per day. Statistically significant associations with PI were observed with regard to sex, living area, and alcohol consumption. PI prevalence in Panama was elevated and showed a sex difference (women: 64.7%, 95% CI: 63.7–66.7%; men: 43.4%, 95% CI: 41.5–47.5%). According to our analysis of three-domain-related physical activities, the main contribution to the total estimated energy expenditure of physical activity/week came from the transport domain, followed by the work/household domain, and the least significant contributor was consistently the domain of exercise- and sports-related physical activities.