Background: There is strong epidemiological evidence that physical activity is associated with lower likelihood of depression. Yet, most existing large population studies have investigated aerobic physical activity (e.g. walking/running), with few epidemiological studies examining the association between muscle-strengthening exercise (MSE; push ups, using weight machines) with depression. The aim of this study is to examine associations between MSE and depressive symptoms among a representative sample of German adults. Methods: Cross-sectional analyses were conducted on the 2014 German Health Update. Validated questionnaires were used to assess MSE and depression symptom severity (eight-item Personal Health Questionnaire Depression Scale). Generalized linear models with Poisson regression with a robust error variance were used to assess prevalence ratios of depression symptom severity (mild, moderate, moderately severe/severe) across weekly MSE frequency (None [reference]; 1, 2, 3–4 and ≥5), adjusting for potential cofounders (e.g. age, sex, socioeconomic status, self-rated health, smoking, hazardous alcohol consumption, aerobic exercise). Results: Data were available on 23,635 adults (≥18 years). When compared with those reporting no MSE, for all levels of depressive symptom severity, there were reduced prevalence ratios across all MSE frequencies. Compared to the higher MSE frequency groups (3-≥5 times/week), the prevalence ratios (range: 0.53–0.85) were similar among lower frequency groups (1–2 times/week) (range: 0.46–0.85). All associations remained after adjustment for sociodemographic, lifestyle characteristics and aerobic physical activity. Limitations: Findings may be biased by the self-reporting of MSE and depressive symptom severity. Conclusion: Any increase in MSE at the population-level may be beneficial for the prevention and treatment of depression