In recent years, river flows have significantly decreased due to regional or global climate change and human activities, especially in the arid and semi-arid regions. In this study, the effects of climate change and human activities on the runoff responses were examined using hydrologic sensitivity analysis and hydrologic model simulation in the Lighvan basin located in the northwest of Iran. The Mann–Kendall test was applied to identify the trends in hydroclimatic data series. Also, the Pettitt test was used to detect change points in the annual discharge values and climatic variables. The results showed that there was negative trend in discharge data series, and examination of the climatic factors indicated that there was an increase in the temperature values and a decrease in the relative humidity values at the basin. The rapid changes in runoff values and most of the climatic variables occurred in the mid-1990s. The effect percentages of the human factors and climatic factors on runoff reduction in all the models used were 65–84% and 16–35%, respectively. Therefore, the impact of human activities on the river flow changes was significant.