A large proportion of Malawi’s more than 13 million people live in rural areas where major livelihood activities include subsistence farming, irrigation and fishing. Therefore the villagers have contact with water, which exposes them to schistosomes. In this case study, surveys and parasitological investigations were conducted to determine the prevalence of schistosomiasis and to explore the relationship between disease prevalence and selected qualitative variables in five villages located in Zomba District in Lake Chilwa Basin. The study revealed a high prevalence, ranging from 23% in Machemba village to 49% in Mukhweya village. Children, 6–15 years old, were the most heavily infested (40%), and the 0–5 years group the least. A high prevalence was observed among school children (39%), and occupations such as irrigated farming (26%) and fishing (24%). Analyses at the 0.05 a-level revealed statistically significant associations between schistosomiasis prevalence and village of residence, age group and occupation type, but there was insufficient evidence to suggest a significant relationship with gender. Based on these findings, targeted awareness and mass treatment programmes were implemented in all the villages, and 9085 people were treated.