Developing and improving environmental audit methodologies is integral to natural resource management. This paper presents an innovative approach to studying and analysing anthropogenic impacts on the territories whose boundaries are limited by the watershed area of a small or medium-sized river. Using geoinformation technologies and high-resolution digital elevation models allowed us to create an accurate geospatial model of anthropogenic transformations of the Oril River watershed area within the Dnipropetrovsk region (Ukraine). The proposed approach to identifying potentially hazardous objects is based on surface slopes and their distance from the riverbed within the watershed area. Based on the modelling results, a refined watershed area of the Oril River with a total area of 11.1 thousand square kilometres was developed. Digitalisation and categorisation of anthropogenically transformed lands allocated for residential development, industrial enterprises, farms, agricultural land, roads, and railways within the Oril River watershed in the Dnipropetrovsk region (3963 km2) were conducted. It was found in the investigation that 79% of the study area comprises anthropogenically transformed land primarily used for agricultural and industrial activities. The modelling results underscore that agricultural activity serves as the principal source of anthropogenic pressure on the ecosystems of the studied area. The proposed improvements to the environmental audit methodology can be used in developing regulations to limit the negative impact of economic activity on the environment. This will ensure the region’s sustainable development and fulfil Ukraine’s obligations to preserve natural resources including international standards. The conclusions of the article point to the need to further improve the tools for assessing anthropogenic impact and planning environmental protection measures.