Major chemical accidents (MCAs) usually cause multiple casualties, property losses, and environmental damage. MCAs in hazardous chemical production enterprises (HCPEs) in China have been frequent in recent years. Understanding past accidents is essential for accident prevention and risk mitigation. However, no accurate statistical analysis and systematic human cause investigation of MCAs in China is available. Hence, this study systematically identified the main characteristics and human factors of MCAs in China during 2011–2022 using official accident investigation reports. First, the 160 MCAs were investigated by mathematical and statistical methods involving eight main characteristics: evolution trend, spatial locations, accident types, domino effects involved, occurrence links, time volatility, hazardous chemicals involved, and enterprise scales. Second, based on the characteristics of MCAs and existing research on chemical accidents, the Human Factors Analysis and Classification System (HFACS) for Chemical Accidents (HFACS-CA), which consists of 26 cause categories and is suitable for the analysis of chemical accidents, was proposed on the basis of HFACS and other extended HFACS. Then, the selected 146 representative MCAs were analyzed using the HFACS-CA framework; the human factors (comprising human and organizational factors (HOFs) and outside factors) of MCAs in China were systematically explored. Finally, according to the main characteristics and human factors of MCAs, comprehensive recommendations for the prevention of MCAs involving enterprises, governments, and interested parties were proposed. This work can provide a useful human factors analysis tool for investigating chemical accidents and valuable information for preventing MCAs in China and other countries.