<p>How to design and organize the various elements of the urban environment to reduce the spread of infectious diseases has long been a central focus of urban planning. However, current spatial investigations into infectious disease transmission typically focus on the broader cityscape at a regional scale, leaving the specific relationship between infectious diseases and urban environments at the neighborhood level largely unexplored. Additionally, the synergistic potential of architecture and landscaping in effectively combating disease transmission remains a topic requiring further investigation. Therefore, this study uses COVID-19 case data from 1500 census tracts in the United States in February 2020 to establish regression models at the neighborhood level to measure the most influential factors and interactive effects between urban morphology and greenery on disease transmission. The findings underscore the significant impact of architectural footprint characteristics, such as square compactness, and natural environment metrics, exemplified by green space, on the propagation of infectious diseases within urban settings. It is also found that reducing the proportion of shared wall ratio can enhance the inhibitory effect of green spaces on disease transmission. These insights offer valuable design recommendations for neighborhood architecture and urban green spaces, enhancing urban resilience to epidemic outbreaks.</p>