We investigated the effect of land use based on the dominant phytoplankton and physical-chemical variables in the different areas of the Tigris River, within the city of Mosul. Agricultural and urban activities have a significant impact on the water quality of the river. Regardless of physical and chemical variables, phytoplankton act as a bio-indicator of water quality due to their fast and sensitive response to changes in the environment. Our research was conducted in the Tigris River within the city of Mosul by examining the phytoplankton species and the physical-chemical variables at 16 sites during each vegetation period. Point and non-point source pollutants have affected the Tigris River within the city of Mosul, getting into the river from upstream through agricultural activities and by urban activities in the middle section of the city, respectively from both banks. Based on our results, we observed the highest phytoplankton abundance during the October sampling periods, while the lowest occurred during the July sampling period, which was associated with maximum water temperature and absence of rain. According to our study, land use (e.g., agricultural, and urban activities) greatly affected the dominant phytoplankton species and physical-chemical variables of the Tigris River. Oscillatoria sp. dominated all seasons in the agricultural region, while at the same time, we observed an increase in the number of phytoplankton species caused by the nutrient availability upstream on the river. The effects of climate have very significant and characteristic effects in this area, which basically determine the community of organisms and the water quality; the effects resulting from anthropogenic activity significantly modify this. Based on our investigation, in the part of the Tigris River connected to Mosul, we found a clear connection between the pollution caused and the effects of different land uses, through the examination of the algal community and physical-chemical variables in different periods of the year.