Land-use change is among the most important human impacts on habitat quality and species diversity. In this study, we investigated the effects of land use on river habitat quality and sediment granulometry in a larger tropical river, affected by urbanization and agricultural land use. We selected 15 representative sampling reaches in the Rio das Mortes basin, 12 of them along the main river from its headwater to its mouth, and 3 in major tributaries. A habitat survey was conducted in these reaches in the dry season 2010 and sediment samples were taken for granulometry analyses. Sub-basin land cover of reaches was dominated by natural vegetation (41.6 to 60.2% of total land cover), followed by agricultural land cover (38.4% to 56.9%) and urban land cover (1.4% to 5.6%). Sediments were dominated by poorly to moderately sorted silts to sands, little conducive to diverse biological communities. According to the river habitat survey, all investigated river reaches exhibited moderately to totally disturbed habitat integrity, due to diverse and often co-occurring human impacts, such as riparian deforestation, water abstraction, sand and gravel extraction, and margin erosion. Only one of the investigated sampling reaches exhibited the minimum riparian forest corridor width demanded by the Brazilian Forest Code. Our results indicated that river habitat and sediment quality mainly depended on conditions in the direct vicinity of river reaches. Accordingly, initial cost-effective restoration of aquatic habitats could be achieved by relatively simple channel restoration measures and the protection of the riparian corridor in the investigated tropical river.