Urban heat island (UHI)-related mortality in different geographical regions remains controversial. In this study, we selected 70 pairs of adjacent urban-rural counties from 8 topographic regions in China. Daily mortality data from 2017 to 2021 were obtained from the mortality surveillance system of China. Daily temperature data were obtained from national meteorological stations located within the boundary of each county. A distributed lag nonlinear model and meta-regression were used to analyze the data. The results showed that the relationship between UHI and heat-related mortality varied across regions in China and could be classified into four categories. Regions with seldom and most frequent heat show lower urban-rural disparities in heat-related mortality. A higher heat risk was observed in urban than in rural areas in the Northeast Plain and Loess Plateau, with a moderate frequency of heat and low air conditioner ownership rate. Conversely, a negative correlation between UHI and mortality was observed in regions with frequent heat and high urban-rural disparity in the air conditioner ownership rate. Similar urban-rural disparities were found in older adults with specific causes. These findings contribute to a better understanding of the impacts of UHI on health and adaptive strategies.