Land use and land cover changes over a 26-year period for the middle Shire River catchment, Malawi, in southern Africa, were assessed using geographic information systems (GIS) and remote sensing techniques. The catchment area under study was divided into two sections, western and eastern sides of the Shire River. High rate of deforestation averaging 4.3% per annum was observed and more pronounced in the western side of the river. Rapid population growth and increase in gross domestic product (GDP) are identified as the major drivers of deforestation and forest degradation due to clearing of vast fields for agriculture, land expansion for urban settlement, and cutting down of trees for wood fuel energy. Deforestation in the middle Shire River catchment has resulted into increased soil loss through erosion causing huge accumulation of sediment at the Nkula B Hydroelectric Power Dam downstream and, consequently, causing serious problems with generation of hydroelectricity. Frequent droughts and floods in the area have drastically affected crop production forcing people into cutting down of trees for charcoal as a livelihood strategy. Combined techniques such as GIS, remote sensing, and socioeconomic factors used in this study could be applied in other places where similar challenges occur.