The rivers of the south-eastern part of the Kaliningrad region: Angrapa, Pissa, Krasnaya, Russkaya are highly vulnerable to natural and anthropogenic impacts, have the first and highest category of fishery purposes, and are distinguished by their transboundary status. Monitoring of the ecological state of watercourses is fragmentary and does not meet modern requirements. In connection with the noted features, they are of great interest for research. For each watercourse, 4 points were identified from the headwaters to the mouth, in which hydrological parameters were measured in the autumn hydrological season and water samples were taken for chemical analysis. The multiplicity of exceeding the MPC for a large list of chemical elements was calculated, the WPI and the corresponding class of water quality in the studied rivers were determined. Mapping was carried out and spatial differentiation of the WPI, the multiplicity of exceeding the MPC for dissolved oxygen, BOD5, nitrites, ammonium, iron, oil products was revealed. The results of the study showed that the water quality in the studied rivers is in an unsatisfactory state. The identified spatial pollution is formed in the traditional way—the quality of water from the source to the mouth is deteriorating. The main indicator that contributes to the pollution of watercourses is oil products, which emphasizes the potential anthropogenic impact (the multiplicity of exceeding the MPC varies in a wide range—from 2.80 to 124.60 (for all samples)). Sharp changes in this indicator occur after watercourses pass through large cities by the standards of the study area. In second place is the iron index, which makes a serious contribution to the overall picture of pollution (excess ratios for iron—from 1.94 to 48.49 (for all samples)), which is due to the high concentrations of this ingredient in the groundwater that feeds the rivers. Biogenic pollutants represented by ammonium and nitrite are evenly distributed, which is presumably due to their agricultural origin (from 1.12 to 11.28 times for ammonium [for 5 out of 16 samples] and from 1.38 to 7.38 for nitrite [for 7 out of 16 samples]).