Climate variability has a strong influence on disease prevalence and subsequently on economic wellbeing of the affected households. In this study, six regions were selected and clustered into three groups based on their climatic conditions as follows: areas prone to droughts, floods and those with relatively good weather. Respondents were interviewed and the effects of prevailing climatic conditions on the prevalence of diseases established. Malaria, respiratory tract infection, typhoid, pneumonia and diarrhoea were the major diseases among the Lake Victoria basin residents. The annual disease frequency per household was highest in Budalang'i, a flood prone region; and lowest in Bomet, a region with relatively good weather. The findings reveal the often unseen subtle effects of adverse climatic conditions on economically vulnerable communities in the Lake Victoria basin (LVB) and elsewhere, and recommends flood/drought prevention and mitigation strategies and awareness creation to better cope with the adverse climatic events.