Land use activities along River Nzoia Drainage Basin, Kenya, include cultivation along the river banks, over grazing, deforestation, draining of wetlands for horticulture, harvesting of sand and brick-making. These activities have brought about changes in soil properties in the drainage basin adversely affecting farming output and the ecosystem in general. Consequently, it is important to understand how the different land use activities influence the soil properties in order to design and implement effective soil management strategies. This study examined the effects of land use practices on selected soil nutrients in Nzoia River Drainage Basin in Bungoma County. Cultivation and grazing were identified as important land use practices, while undisturbed sites were treated as controls. Land use practices along the river were identified by actual surveying of the study area. Secondary data on land use practices were obtained from technical reports, from local authorities and government offices. Soil samples were collected from different land use areas using randomly placed 5mx5m quadrats. Solis were collected at depths of 15cm in zigzag grid layout in each sample quadrat using soil auger. A total of 72 soil samples were collected in the study sites and analyzed for total nitrogen (N), available phosphorus (P) and organic carbon (C). Analysis of variance and correlation were performed to determine the significant land use practices affecting soil N, C and P. Cultivation had a significant effect on soil organic C mean value of 1.91 but negatively correlated with total Nitrogen and soil C while undisturbed sites exhibited positive correlation with C (P≤ 0.05). On the basis of our findings, it is recommended that conservation agriculture be practiced in the River Nzoia and its drainage system.