This study explored drug abuse, human agency, and farm labour productivity and their implications for crop production and household food security among smallholder farmers in Southeast Nigeria. The study was necessitated by the belief that drug abuse, if left uncontrolled, could affect the decision-making and labour productivity of farmers, which in turn could constrain crop production and household food security. This study employed a philosophical and empirical approach by evaluating the normative and descriptive aspects of the research problem. The survey design was adopted for the study by selecting 450 respondents from Southern Nigeria using the descriptive survey research design. Data collected were analysed using frequency counts, percentages, mean and standard deviation. The results indicated that the respondents perceived drug abuse as having adverse effects on crop production and agricultural activities, with a grand mean score of 2.98, which was interpreted as negative. The major effects of drug use and abuse on farm activities were decreased concentration, productivity, and efficiency, delay in farm activities, farm accidents, low income from farm produce, and post-harvest losses. Farm labour productivity was perceived to have a positive effect on household food security with a grand mean score of 3.09. The results further revealed the extent to which human agency played a role in decision-making in relation to drug use and agricultural production activities. Farm labour productivity was influenced by personal skills and competencies, access to resources such as credit facilities, and other farm inputs. About 84.4% of the respondents agreed that farmers have the capacity to decide how farm labour could be allocated to farm activities, while 75.6% of the respondents indicated that farmers have the ability to decide whether to take drugs before engaging in farm activities. Human agency was however, constrained by the lack of access to extension services, counselling and treatment services among farmers in Southeast Nigeria. The major socioeconomic variables associated with drug use and abuse among farmers were farm-related stress, poverty, availability of drugs, strenuous farm activities, and lack of government intervention. The study concluded that the prevention and control of substance abuse among smallholder farmers require a concerted effort in promoting personal responsibility while encouraging the provision of treatment services and other enabling environments for curtailing the spread of substance abuse among farmers. The study recommends a holistic agricultural policy that targets substance-abuse prevention, agricultural extension services, and rural health services in addition to policies that promote farm labour productivity, crop production, and household food security. The study further recommends the need for promoting sustainable agricultural production and appropriate livelihood options among smallholder farmers in Southeast Nigeria.