Air pollution and heat are significant threats to public health, especially in urban areas with intensive human activities under the trend of climate change. However, the mediation effects of urban form on health via air pollution and heat have been overlooked in previous investigations. This study explored the potential impacts and pathways of urban form on cardiovascular mortality through air pollutants and heat by using partial least squares model with data from Taiwan. The measurable characteristics of urban form include city size, urban sprawl, and mixed land use. Other factors that influence cardiovascular mortality, such as urban industrial level, economic status, aging population, and medical resource, were also considered in the model. Results revealed that maximizing mixed land use and minimizing city size and urban sprawl can help reduce cardiovascular mortality, and the minimizing city size was the most important one. Urban industrial level, economic status, aging population, and medical resource were also influential factors. This is the first study to consider the pathways and impacts of urban form on cardiovascular mortality, and our results indicate that proper urban planning and policy could reduce cardiovascular mortality.