House construction is rapidly modernizing across Africa but the potential benefits for human health are poorly understood. We hypothesised that improvements to housing would be associated with reductions in malaria, acute respiratory infection (ARI) and gastrointestinal illness in an area of low malaria endemicity in Uganda. Data were analysed from a cohort study of male and female child and adult residents (n = 531) of 80 randomly-selected households in Nagongera sub-county, followed for 24 months (October 4, 2017 to October 31, 2019). Houses were classified as modern (brick walls, metal roof and closed eaves) or traditional (all other homes). Light trap collections of mosquitoes were done every two weeks in all sleeping rooms. Every four weeks, we measured malaria infection (using microscopy and qPCR to detect malaria parasites), incidence of malaria, ARI and gastrointestinal illness. We collected 15,780 adult female Anopheles over 7,631 nights. We collected 13,277 blood samples of which 10.2% (1,347) were positive for malaria parasites. Over 958 person years we diagnosed 38 episodes of uncomplicated malaria (incidence 0.04 episodes per person-year at risk), 2,553 episodes of ARI (incidence 2.7 episodes per person-year) and 387 episodes of gastrointestinal illness (incidence 0.4 episodes per person-year). Modern houses were associated with a 53% lower human biting rate compared to traditional houses (adjusted incidence rate ratio [aIRR] 0.47, 95% confidence interval [CI] 0.32-0.67, p<0.001) and a 24% lower incidence of gastrointestinal illness (aIRR 0.76, 95% CI 0.59-0.98, p = 0.04) but no changes in malaria prevalence, malaria incidence nor ARI incidence. House improvements may reduce mosquito-biting rates and gastrointestinal illness among children and adults. For the health sector to leverage Africa's housing modernization, research is urgently needed to identify the healthiest house designs and to assess their effectiveness across a range of epidemiological settings in sub-Saharan Africa.