Background: In recent decades, accidents involving hazardous goods at seaports have become a major concern worldwide resulting in international conventions and interventions to minimise the impact of such accidents. Despite the improvements in safety measures and the enhancement of cargo handlers’ knowledge over the years, port accidents involving dangerous substances still continue to occur.Objectives: The study explores the determinants of effective high-risk cargo (HRC) handling at seaports, focusing on Namibian seaports. The study was aimed at establishing the elements of HRC logistics processes and to determine factors influencing the effectiveness of HRC handling procedures followed by the seaports.Method: An integrated research strategy was adopted, backed by the employment of mixed research methods, through seven key informant interviews and a quantitative survey involving 81 port employees.Results: The results of the study confirmed the totality of HRC logistics activities at Namibian seaports. It emerged from the study that there were factors that facilitated and that hindered the effectiveness of HRC logistics activities at Namibian seaports. The study confirmed the association between HRC training and the level of knowledge of risk mitigation and emergency procedures, documentation understanding and regulations adherence. This guided in proposing a new theory for the determinants of HRC logistics in developing economies.Conclusion: The study’s findings provided sufficient evidence to suggest that HRC logistics safety processes at seaports can be improved through the proposed framework. The study’s findings have important repercussions for re-shaping public policy, especially as coastal economies worldwide compete towards becoming preferred logistics hubs.