Resilience describes a good adaptation to adversity. Strengthening resilience is a promising approach in the prevention of mental health problems. Yet, research on the association of resilience with mental health symptoms in the general population is scarce. The aim of our study is to examine comprehensively the association of resilience with depressive symptoms, anxiety, and perceived stress in a large population-based sample. We analyzed data of n = 3762 participants from the follow-up assessment of the LIFE-Adult-Study, a population-based cohort study in Leipzig. Assessments included resilience (RS-11), depressive symptoms (CES-D), anxiety (GAD-7), and perceived stress (PSQ). The association of resilience with mental health symptoms was examined via multiple linear regression analyses. In our analyses, higher resilience predicted less mental health problems and contributed significantly to the explained variance in mental health outcomes. Women, individuals with previous mental disorders, and those without employment had higher mental health symptoms. Resilience is closely associated with mental health problems in the general population. Vulnerable groups should be targeted with public health measures. Strengthening resilience is a promising approach in the large-scale prevention of mental disorders.