Urban floods have long-term mental health implications, yet this subject remains largely neglected in flood-related studies. This paper examines the psychological distress (PD) of adults exposed to floods in Ghana. Cross-sectional data involving 767 flood-prone community-dwelling household heads aged ≥20 years were analyzed [mean = 47.3 years (SD = 13.7); males = 61.4%]. We used the Exposure to Flood-related Events Scale, and PD was assessed with the Kessler Psychological Distress Scale (K10). Ordinary Least Squares (OLS) regressions evaluated crude and adjusted associations of flood exposure with PD. The mean scores of PD (37[SD = 8]) and exposure to flood events (6[SD = 3]) significantly varied by age and sex (p < .05). After full adjustment for potential confounders, exposure to flood events was significantly and positively associated with PD index in the total sample (β = 0.030; p < .005), among male participants (β = 0.019; p < .05) and female participants (β = 0.048; p < .001). Furthermore, age-wise analysis revealed significant association of flood exposure with PD in young adults (β = 0.033; p < .001) but not in older adults (β = 0.048; p = .062). Exposure to floods increased the risk of PD. Policy and public health efforts to manage PD should include selective flood reduction interventions, including land use regulations and sustained public education.