Human factors/errors (such as inappropriate actions by operators and unsafe supervision by organizations) are a primary cause of oil spill incidents. To investigate the influences of active operational failures and unsafe latent factors in offshore oil spill accidents, an integrated human factor analysis and decision support process has been developed. The system is comprised of a Human Factors Analysis and Classification System (HFACS) framework to qualitatively evaluate the influence of various factors and errors associated with the multiple operational stages considered for oil spill preparedness and response (e.g., oil spill occurrence, spill monitoring, decision making/contingency planning, and spill response); coupled with quantitative data analysis by Fuzzy Set Theory and the Technique for Order Preference by Similarity to Ideal Solution (Fuzzy-TOPSIS) to enhance decision making during response operations. The efficiency of the integrated human factor analysis and decision support system is tested with data from a case study to generate a comprehensive priority rank, a robust sensitivity analysis, and other theoretical/practical insights. The proposed approach improves our knowledge on the significance of human factors/errors on oil spill accidents and response operations; and provides an improved support tool for decision making.