Monitoring and protecting flowing watercourses is a complex and challenging task that requires the collaboration and coordination of various stakeholders such as governments, industries, farmers, consumers and environmental groups. The study of the dynamics of the concentration of polluting factors and especially the concentrations of heavy metals and highlighting a seasonal variation is a necessary element from this point of view. In this article, we present the results of our analyses carried out in two measurement campaigns executed in 10 monitoring points along the Danube River, between Braila city and Isaccea city in the pre-deltaic area, during the summer season and autumn season 2022. The importance of this area is given by the fact that the Danube Delta is part of the UNESCO heritage, and the monitoring of polluting factors is a necessity in the desire to protect this area. The data measured during the July and August 2022 campaign cover a wide range of chemical species: Phosphate, CCO, CBO5, NH4+, N-NO2, N-NO3−, N-Total, P-PO4 3−, SO42−, Cl−, phenols, as well as metals with a harmful effect: Al, As, Cd, Cr, Fe. The study includes an evaluation based on the statistical approach of the results to highlight the significant correlations and differences identified between the two data sets. Next, to highlight the obtained results, a numerical model was considered using HEC-RAS and ESRI ArcGIS applications in a two-dimensional unsteady flow model in order to obtain the non-homogenous concentrations’ distributions in the studied area. These two-dimensional models have been less studied in the specialized literature. In this way, interesting results could be obtained, and prediction methods regarding the dynamics of metal concentrations could be structured. The data obtained were used for the terrain model from the USGS service, and the flows of the Danube and its two tributaries were simulated using the data provided by the national services. In this work, we present the results obtained for the dynamics of the concentrations of the metals Al, As, Cd, Cr and Fe and the evaluation of the specific absorption coefficients for the explanation and correlation with the results of the measurements. Except for the numerical model presented, we would like to highlight the existence of some contributions of the main tributaries of the Danube in the study area. Such a systematic study has not been carried out due to conditions imposed by the border authorities. From this point of view, this study has an element of originality. The study is part of a more complex project in which the spatio-temporal distribution of the polluting factors in the water was evaluated, and the habitats in the study area were inventoried—especially those of community interest. In this way, we were able to expose the self-purification capacity of the Danube and highlight the existence of a concentration reduction gradient along the course of the river. The aspects related to the influence of the distribution of polluting factors on the state of health will be the subject of another article.