Despite a clear distinction between aerobic and muscle strengthening (MS) components in the physical activity guidelines, public health surveillance has largely focused only on aerobic components, limiting the reach of epidemiological research on the physical activity guidelines. Hence, this study investigated the association between adherence to both components (i.e. aerobic and muscle-strengthening) of the World Health Organization's physical activity guidelines and mental health among the college student population. A cross-sectional study was conducted among a nationally representative sample of Irish college students (7088 participants, M age: 23.17 years; 50.9% female). Participants were categorized as meeting both components of the guidelines (n = 41%), only the aerobic component (n = 25.3%) or the MS component (n = 7.3%), and neither (n = 26.4%). Group membership effects on mental health was determined through mixed univariate ANOVAs, with a Bonferroni correction for post hoc analyses to assess multiple comparisons. Results revealed that meeting both components of the guidelines was significantly (all p < 0.01) associated with greater self-reported happiness, body image and general health, and less mental ill-being, relative to all other respective groupings. Meeting aerobic or MS components in isolation was significantly (p < 0.05) associated with better happiness, general health and body image compared to not meeting either component. To conclude, 59% of the college-aged population are insufficiently active, and adherence to both guideline components is positively associated with mental health. Co-produced, evidence-based, physical activity interventions are needed in students and could contribute to mental health promotion.