Conserving clean and safe freshwater is a global challenge, with nitrogen (N) and phosphorus (P) as frequent limiting factors affecting water quality due to eutrophication. This paper provides a critical overview of the spatiotemporal variability in both nutrient concentrations and their total mass ratio (TN:TP) in the canal network of the Hydro system Danube–Tisza–Danube at 21 measuring locations monitored by the Environmental Protection Agency of the Republic of Serbia over a length of almost 1000 km, collected once a month during the last decade. A spatiotemporal variation in nutrient concentrations in the tested surface water samples was confirmed by correlations and cluster analyses. The highest TN concentrations were found in winter and early spring (non-vegetation season), and the highest TP concentrations in the middle of the year (vegetation season). The TN:TP mass ratio as an indicator of the eutrophication pointed out N and P co-limitation (TN:TP 8–24) in 64% of samples, N limitation (TN:TP < 8) was detected in 27% and P limitation (TN:TP > 24) in the remaining 9% of water samples. Such observations indicate slow-flowing, lowland water courses exposed to the effects of non-point and point contamination sources as nutrient runoff from the surrounding farmlands and/or urban and industrial zones, but further investigation is needed for clarification. These results are an important starting point for reducing N and P runoff loads and controlling source pollution to improve water quality and underpin recovery from eutrophication in the studied watershed.