The Senqu-Orange basin is the principal carrier of the mean annual runoff for the larger portion of South Africa, also encompassing Lesotho. The transformation of this river regime by inter-basin transfer from south-westerly flowing rivers to the northerly flowing Senqu-Orange system of water as a resource may have adverse impacts on freshwater quality of ecosystems. This work presents a case study of the Lesotho Highlands Water Project, investigating alterations of the physical and chemical water quality caused by large infrastructure: Mohale Dam; Katse Dam and Matsoku Weir; and a delivery tunnel from ’Muela Dam to the Ash River. The aim of the study was to determine significant differences, if any, of selected water quality variables in water released or transported from these infrastructure. In this book, the results are evaluated using time series graphs and various statistical methods against the overall question: Have the large infrastructure altered the physical and chemical water quality of the Senqu River system? The findings of this study should assist with the environmental management of the civil engineering projects implemented in or nearby freshwater rivers.