Land cover changes (LCC) affect the water balance (WB), changing surface runoff (SurfQ), evapotranspiration (ET), groundwater (GW) regimes, and streamflow (Q). The Tapajós Basin (southeastern Amazon) has experienced LCC over the last 40 years, with increasing LCC rates projected for the near future. Several studies have addressed the effects of climate changes on the regions hydrology, but few have explored the effects of LCC on its hydrological regime. In this study, the Soil and Water Assessment Tool (SWAT) was applied to model the LCC effects on the hydrology of the Upper Crepori River Basin (medium Tapajós Basin), using historical and projected LCC based on conservation policies (GOV_2050) and on the Business as Usual trend (BAU_2050). LCC that occurred from 1973 to 2012, increased Q by 2.5%, without noticeably altering the average annual WB. The future GOV_2050 and BAU_2050 scenarios increased SurfQ by 238.87% and 300.90%, and Q by 2.53% and 2.97%, respectively, and reduced GW by 4.00% and 5.21%, and ET by 2.07% and 2.43%, respectively. Results suggest that the increase in deforestation will intensify floods and low-flow events, and that the conservation policies considered in the GOV_2050 scenario may still compromise the regions hydrology at a comparable level to that of the BAU_2050.