Attitudes toward COVID-19 (coronavirus disease 2019) prevention and control may have influenced general practitioners’ (GPs’) work during the COVID-19 pandemic. The present study aimed to investigate the attitudes and practices of GPs from Croatia and Bosna and Herzegovina regarding COVID-19 prevention and control as well as the factors which may have influenced them. A cross-sectional study using a self-administered, anonymous questionnaire was conducted between February and May of 2022 on 200 Croatian and Bosnian GPs. The study revealed that the attitudes and practices of the surveyed GPs regarding COVID-19 prevention and control were satisfactory. The Croatian GPs reported a larger number of positive attitudes toward COVID-19 prevention and control (p = 0.014), while no significant differences in practices were established. Among the Croatian GPs, more positive attitudes toward COVID-19 prevention and control were reported by participants who had finished a formal education on the prevention of infectious diseases and occupational safety (p = 0.018), while among the Bosnian GPs, more positive attitudes were reported by older GPs (p = 0.007), males (p = 0.026), GPs with a longer length of service (p = 0.005), GPs who had finished a formal education on the prevention of infectious diseases and occupational safety (p < 0.001), GPs who had finished a formal education on adequate hand hygiene (p < 0.001), and GPs who had finished a formal education on COVID-19 prevention for GPs (p = 0.001). Considering GPs’ practices regarding COVID-19 prevention and control, among the Croatian GPs, more positive practices were reported by older GPs (p = 0.008), females (p = 0.002), GPs who had a partner (p = 0.021), GPs who were specialists in family medicine (p = 0.014), GPs with a longer length of service (p = 0.007), and GPs who had finished a formal education on the prevention of infectious diseases and occupational safety (p = 0.046), while among the Bosnian GPs, no significant correlations were determined. The general practitioners’ sociodemographic and employment characteristics strongly influenced their attitudes and practices regarding the prevention and control of COVID-19. The cultural differences between Croatia and Bosnia and Herzegovina, as well as the organizational specificities of their healthcare systems, probably modified the observed differences in the individual patterns of associations between the outcome and explanatory variables in the surveyed neighboring countries.