Nigeria is the single largest producer of cassava in the world with the bulk of the cassava coming out from the Niger Delta region. Human, economic and agricultural activities are currently threatened in the region by vagaries in climatic factors. These vagaries affect the production and profitability of cassava. The study was therefore conducted to assess the effects of climate change on the production and profitability of cassava in the Niger Delta region of Nigeria. The study made use of a multi-stage sampling technique to select three hundred and sixty respondents across the three highest cassava-producing states (Awka Ibom, Cross Rivers and Ondo) in the region. Data for the study were collected with the aid of well-structured questionnaires assisted with interview schedules. Data collected were analysed using descriptive statistics and regression model. The determinants of cassava profitability were farm size, farmers’ experience in cassava cultivation, farmers’ experience in adopting climate change coping strategies, number of climate change coping strategies adopted, costs of input materials in Naira and labour cost in Naira.