Previous studies have suggested that mindfulness can protect the well-being of socioeconomically disadvantaged individuals. This article examines the mediating roles of resilience and perceived discrimination in the relationship between mindfulness and well-being (including life satisfaction and psychological distress) among socioeconomically disadvantaged college students. A questionnaire was administered to 919 socioeconomically disadvantaged undergraduates (48% females, aged 17–25). According to the results of structural equation modeling, mindfulness was positively associated with life satisfaction and negatively associated with psychological distress. These two relationships were mediated along three pathways: higher resilience, lower perceived discrimination, and the sequential pathway from higher resilience to lower perceived discrimination. These results suggest that mindfulness is positively related to greater life satisfaction and negatively related to psychological distress among socioeconomically disadvantaged college students by enhanced resilience and decreased perceived discrimination. The findings can be applied to the design of mindfulness-based psychological health care services for socioeconomically disadvantaged populations.