The SARS-CoV-2 pandemic is now expanding into the developing world with devastating consequences. Departing from a population-based study in rural Ecuador where all adult individuals (aged 40 years or older) were tested for SARS-CoV-2 IgG and IgM antibodies, we expanded it to include a house-based case–control component assessing in-house clustering and other variables potentially associated with infection. We selected houses where exactly two study participants lived and were both seropositive (case-houses), and matched 1:1 to control-houses where both were seronegative. Younger household members had an antibody test performed. Infected household members were found in 33 (92%) case-houses and in only six (17%) control-houses. In 28/29 discordant house pairs, the case-house had seropositive household members and the control-house did not (odds ratio: 28; 95% CI: 4.6–1,144). Our data demonstrate strong in-house clustering of infection in community settings, stressing the importance of early case ascertainment and isolation for SARS-CoV-2 control.