Background: Non-communicable chronic diseases (NCDs) have become the top threat in China. This study aimed to estimate the prevalence of major NCDs among the elderly population in rural areas in southern China and explore its associated social determinants. Methods: A multistage cluster random sampling methodology was adopted to select a total of 9245 rural elderly people from 3860 rural households in Guangdong Province. Interviews and physical examinations were performed to collect patient information. Descriptive and logistic regression analyses were conducted to explore factors associated with the presence of major NCDs. Results: Over one-third (38.5%) of the study population suffered from five major NCDs. The grade of activities of daily living (ADL), mental status, and social relationship of elderly people without NCDs were better than those with NCDs. The major factors associated with the presence of NCDs among the elderly people included age (70–79 years group and 80–89 years group), education level (senior high/technical secondary school and junior college and above), mental status (concentration, enrichment and happy life and memory), relationship with neighbours, activities of daily living (ADL) (being able to climb three floors and bend over), physical activity, marital status (bereft), and living conditions (with offspring and family members). Conclusions: The study identified several social determinants associated with the presence of major NCDs. A higher level of family support and physical exercise might contribute to improved physical condition, mental status, and ADL among the elderly people in rural areas in southern China.