The Usangu wetland (Ihefu) is a wetland of great importance for its biodiversity and acts as regulator for downstream flows for the Great Ruaha River through the Ruaha National Park. While recognizing the importance of this wetland, little is known about the effects of land use and cover changes on the wetland itself and the flow regime of the Great Ruaha River in the downstream. Recognizing that, a study was conducted using remote sensing and GIS techniques to inventory land use/cover changes in the watershed over the years. Hydrological data were analyzed to reveal the alterations and trends at three periods (pre-1974, 1974-1975 and post 1985) from 1958 to 2004. It was revealed that there was a steady increase in cultivated area, from 121.2 km2 to 874.3 km2 between 1973 and 2000 while the woodland area decreased significantly over years. The minimum dry season area of the wetland declined significantly, with more changes occurring between 1984 and 2000 at 67% reduction. The river was found to be sensitive to land use/ cover changes and highly variable on an intra annual (seasonal) and inter-annual (year to year) basis. There was a slight shift in the peaking for the post-1985 period with high flows attained earlier in February instead of April. The Q50 flow progressively declined from 19.23m3s-1 in the pre-1974 to 16.51 m3s-1 and 9.04 m3s-1 for 1974-1975 and post-1985 period respectively. The Q95 (low flow) declined from 2.84 m3s-1 to 0.11 m3s-1 and 0.0 m3s-1 for pre-1974, 1974-1975 and post-1985 period respectively. The study concludes that the modification of the land use and cover has resulted into changes in time distribution of runoff within the catchment. The study highlights the effects of land use /cover changes on ecosystems and water resources for an informed decision on proper catchment planning and management.