Rapid urbanization has caused widespread environmental pollution in Africa, restricting sustainable development programs. Today, non-point source pollution has become a major threat to many African cities. In this study, we have classified urban land use followed by the identification of urban functional areas based on multi-source data. We have then evaluated non-point source pollution based on nitrogen and phosphorus loads at a spatial scale in Mwanza city (Tanzania). We have estimated the spatial distribution of total nitrogen (TN) and total phosphorus (TP) loads at a scale of 1 square kilometer grid. The results show that ① the built-up area of the city was identified as 28.9 km2, accounting for 6.8% of the total area of the city. The area of informal settlements was 56.9 km2, accounting for 13.4% of the total area of the city. About 90.38% of 2.41×105 kg of the total TN load and 87.23% of 4.00×104 kg of the total TP load in the city were derived from the informal settlements alone in 2020. ② The average load intensities of TN and TP in Mwanza city were 6.90 kg·hm-2·yr-1 and 1.14 kg·hm-2·yr-1, respectively. The average TN and TP intensities in Mwanza city were slightly higher than the average TN and TP load intensities in the Lake Victoria basin. However, given the high population density of the Mwanza city area, the average TN and TP intensities were found to be consistent. ③ The TN and TP pollution loads were relatively concentrated in the inner urban area, including the lower reaches of the Mirongo River basin, the eastern side of the Nyamagana Peninsula, and the lakeside area extending north and south from the peninsula, and gradually decreased toward the city’s outskirts. We propose that the identified riparian areas in our study should be prioritized as potentially key construction zones for pollution treatment plant facilities and urban renewal pilot programs for restraining the widespread informal settlements. This study contributes to the development of an innovative urban non-point source pollution control measure, which may be applicable to low-income countries in Africa and elsewhere.