The aim of this study was to assess gender differences in the prevalence non-communicable diseases (NCDs) and in associated health-related habits, weight status and common risk factors in Botswana. Data were from the cross-sectional, population-based Botswana STEPS Survey II conducted in 2014. A total sample of 2947 survey participants aged 25–64 years were included the study. The results showed that a statistically significant higher percentage of men used tobacco compared with women (34.4%, 95% CI: 33.5–35.1 vs 4.4%, 95% CI: 4.3–4.5). Men also had consistently and statistically significantly greater heavy alcohol consumption and lower fruit and/or vegetable consumption than women. Physical inactivity among women was higher than in men. Controlling for other factors, men had a higher probability of being overweight (28.7%, 95% CI: 28.6–28.8 vs 18.3%, 95% CI: 18.0–18.6) and obese (25.8%, 95% CI: 25.4–26.2 vs 10.2%, 95% CI: 9.9–10.5) than women. Women were at a greater risk of developing NCDs compared with men since their adjusted prevalence of having at least three common risk factors was higher than men’s. Women had a higher adjusted predicted prevalence of suffering from hypertension than men (39.4%, 95% CI: 38.9–40.0 vs 26.1%, 95% CI: 25.5–26.8). Appropriate policies and programmes need to be adopted to urgently address the problem of NCDs in Botswana.