Housing quality has been identified as a key factor for malaria transmission risk. Here, we study the macroecological association between housing quality, measured by construction materials, and water access with malaria transmission at the county level in Costa Rica. We used SCAN cluster analysis to identify spatio-temporal clusters of malaria transmission using county level annual malaria records from 1976 to 2018. Data on housing materials and water access collected in the 1973, 1984, 2000 and 2011 national population censuses were analyzed using principal component analysis to derive housing quality and water access indices at the county level. Negative binomial rate generalized linear models, and Akaike Information Criterion (AIC) based model selection, were used to study the association between malaria cases and the percent of houses with metallic roofs, housing quality and water access indices. We found that Malaria was clustered in southern Huétar Caribe Region (Relative Risk, RR = 62.61 for 1990–2008), Huétar Norte Region (RR = 13.73, for 1991–2000) and Puntarenas county (RR = 5.77, for 1995–2002). From 1984 to 2011 most of the counties where malaria was clustered were in the lowest 20th percentile of housing quality in Costa Rica. The regression analysis showed that malaria cases significantly decreased with increasing housing quality at rates that accelerated through time. Our results suggest that housing quality improvement is one among several factors that led Costa Rica to the malaria pre-elimination stage. We propose that housing quality improvement should be considered a component of long-term policies aiming to reduce, or eliminate, major vector-borne and other neglected tropical diseases from Costa Rica, regionally in Mesoamerica, and globally elsewhere. • We studied malaria case clusters in Costa Rica from 1976 to 2018. • Areas where malaria clusters were observed also had some of the worse housing quality. • Overall, as housing quality improved, malaria cases diminished in Costa Rica. • Our results suggest that housing quality improvement policies should be an integral part of malaria elimination strategies. [ABSTRACT FROM AUTHOR]