The accessibility of urban rail systems in residential areas significantly impacts residents’ overall life satisfaction. Although many studies have examined the overall impact of rail accessibility on life satisfaction in various developed countries, few have focused on spatial heterogeneity and travel ability between rail accessibility and life satisfaction in developing countries. This study uses data from a 2017 activity-travel survey in Shanghai to examine the relationship between rail accessibility and residents’ life satisfaction in central urban and suburban areas with different travel abilities. It finds that both residential location and travel ability influence the impact of rail accessibility on life satisfaction. There are differences in the thresholds for rail accessibility among residents with different residential locations and private car ownership. These findings suggest that rail transit is a powerful tool for promoting the well-being in developing countries, and proper planning of rail station siting and land use is needed.