A number of cross-sectional studies have suggested that physical activity (PA) is negatively associated with psychological distress in adulthood. A paucity of regionally representative and longitudinal studies has considered this relationship. This study investigated the association between leisure time light and moderate-vigorous PA (MVPA) and psychological distress over 13 years in a regionally representative sample. A total of 4754 men (mean age: 47.2 years) and 5571 women from (mean age: 46.9 years) the Tromsø Study were followed for 13 years. Light PA and MVPA was captured at baseline and psychological distress was captured using the Hopkins Symptom Check List-10 scale. Ordinary least square and Poisson regression models were used, adjusting for multiple confounders to investigate the relationship between light PA/MVPA and psychological distress. In the fully-adjusted model, accounting sociodemographics, history of parental psychopathology, socioeconomic status, marital status, smoking, social support and risk factors, we found evidence that both light PA (β 0.11, 95% CI: 0.03, 0.19; p < 0.01) and MVPA (β 0.19, 95% CI: 0.12, 0.26; p < 0.001) confered protection against psychological distress at follow-up. Among men, a lower MVPA was associated with 14% (RR = 1.14, 95% CI: 1.01, 1.28) increased risk of clinically significant psychological distress; while among women, the risk was 15% (RR = 1.15, 95% CI: 1.06, 1.26; p < 0.001). In this regionally representative cohort, our study suggests that both higher levels of light PA and MVPA confer protection against future psychological distress. However, a key limitation of this study is that psychological distress at baseline was not controlled-for.