Background: From March to April 2019, a flood occurred in several regions of Iran. The most affected provinces were Golestan, Lorestan, and Khuzestan. Aims: The present study aimed to determine the prevalence and determinants of psychological distress and depression among the affected adult population 6 months after the event. Methods: A cross-sectional household survey with face-to-face interview was carried out on a random sample of 1,671 adults aged above 15 years living in the flood-affected areas from August to September 2019. We applied GHQ-28 and PHQ-9 for the assessment of psychological distress and depression, respectively. Results: The prevalence of psychological distress and depression were 33.6% (95% CI [29.5, 37.7]) and 23.0% (95% CI [19.4, 26.7]), respectively. Determinants of psychological distress were a history of mental disorders (Adjusted odds ratio [AOR] = 4.7), primary (AOR = 2.9) or high school (AOR = 2.4) education (vs. university), no compensation received (AOR = 2.1), high damage to assets (AOR = 1.8), the house flooded more than 1 m (AOR = 1.8), female gender (AOR = 1.8), and limited access to health care services (AOR = 1.8). Determinants of depression were unemployment (AOR = 5.3) or being a housewife (AOR = 2.7), a history of mental disorders (AOR = 4.1), high damage to assets (AOR = 2.5), no compensation received (AOR = 2.0), the house flooded more than 1 m (AOR = 1.8), limited access to health care services (AOR = 1.8), and high wealth index (AOR = 1.7). Conclusion: The results of this study revealed a high prevalence of psychological distress and depression in the flood-affected adult population. The high-risk group, particularly flood victims who had a history of mental disorders, and those exposed to severe damages of flood, should be prioritized for screening, and mental health services.