Climate-induced floods are increasing in Africa. The need to evolve framework for adaptation to climate change impact (CCI) among flood-prone fish farmers necessitated this study. Based on availability, 60 farming active flood-experienced fish farmers were purposively selected from flood-prone (Gulu and Kibuku) regions in climate hotspot Uganda. These were assessed for CCI adaptation tendencies in their socioeconomics and farming operation/techniques (FOI) indices, CCI awareness, CCI adaptation strategies, and perceived required interventions (RIs) using structured questionnaire. Data were analyzed through descriptive and multivariate regression tools. Respondents were mostly male, adults, educated, Christian, married, medium-sized family, social group members, 1–5 years’ experience, medium-sized farms, and government trained. Income was 1.0–6.0 million Ugx/year. In FOI, semi-intensive culture system, use of rainwater plus groundwater, small-sized (< 0.5 ha) ponds, ponds possession of inlets and outlets, seasonal farming and mixed culture/farming dominated. Most respondents were aware of CCI, while erratic rainfall with floods and prolonged drought mostly impacted farming. AS-Adaptation Strategy were changed stocking time and livelihood diversification. Communication technology and social group’s membership enhanced adaptation, while inadequate awareness constrains adaptation. Respondents’ RI(s) were tree planting, irrigation and pond perimeter trenching. Gender, government training, farm size, water sources and presence of inlet and outlets in ponds (FOI) predicted adaptation (R = 0.802, R2 = 0.64, P < 0.05). Some socioeconomic, technical and awareness indices could assist CCI flexibility. However, the statistically significant predictors of adaptation, identified adaptive strategies, constraints to adaptation and required interventions could be integrated into a framework for effective CCI adaptation for sustainable fish farming in flood-prone scenarios.