Knowledge management and knowledge assets have gained much prominence in recent years and are said to improve organizational performance. However, the effects of knowledge management practices on organizational performance are not well known, particularly with respect to the newly established universities in the East African region. The aim of this study was to investigate the effects of knowledge management practices on organizational performance at selected campuses of Kisii University in the South-western part of Kenya. The knowledge management practices identified were knowledge capture and acquisition, knowledge sharing, and knowledge management policies and strategies. The study established that knowledge management practices have a strong and positive effect on organizational performance. Hoarding of knowledge by members of staff was the major knowledge management challenge identified. Recommendations and areas for further studies are indicated.