This study investigates the ability of the regional climate model Weather Research and Forecasting (WRF) in simulating the seasonal and interannual variability of hydrometeorological variables in the Tana River basin (TRB) in Kenya, East Africa. The impact of two different land use classifications, i.e., the Moderate Resolution Imaging Spectroradiometer (MODIS) and the US Geological Survey (USGS) at two horizontal resolutions (50 and 25 km) is investigated. Simulated precipitation and temperature for the period 2011–2014 are compared with Tropical Rainfall Measuring Mission (TRMM), Climate Research Unit (CRU), and station data. The ability of Tropical Rainfall Measuring Mission (TRMM) and Climate Research Unit (CRU) data in reproducing in situ observation in the TRB is analyzed. All considered WRF simulations capture well the annual as well as the interannual and spatial distribution of precipitation in the TRB according to station data and the TRMM estimates. Our results demonstrate that the increase of horizontal resolution from 50 to 25 km, together with the use of the MODIS land use classification, significantly improves the precipitation results. In the case of temperature, spatial patterns and seasonal cycle are well reproduced, although there is a systematic cold bias with respect to both station and CRU data. Our results contribute to the identification of suitable and regionally adapted regional climate models (RCMs) for East Africa.