The Minjiang River, a typical tidal channel in Southeast China, plays an important role in the supply of drinking water, flood control and drought relief, farming and navigation, as well as shipping and other functions. Dissolved oxygen (DO), as a basic living condition for aquatic biota, has been deteriorating in the Minjiang River in recent years. In order to understand how the spatial distribution of DO responds to river discharge, nutrient loading and water temperature, a three-dimensional Environmental Fluid Dynamics Code model was used to simulate water age and the distribution of DO in the Minjiang River. The model presented in this paper was used for water resource and water quality simulations under various physical, chemical, and biological scenarios. Sensitivity simulation results indicated that the three factors had a significant impact on the spatial distribution variation of DO in the Minjiang River. Increased river discharge or split ratio of the North Channel resulted in decreased water age and increased DO. Increased nutrient loading and water temperature caused lower DO. In order to protect coastal environments in the Minjiang River, river discharge should be increased and pollutants of local cities should be reduced during the high temperature and drought period.