We report epidemiological and clinical aspects of an outbreak of louse-borne relapsing fever (LBRF) in Asella in Arsi Zone, central Ethiopia, from July to November 2016. A total of 63 LBRF cases were reported. The overall case fatality rate was 13% among treated patients. In this article, the first-line epidemiological assessment, individual prevention and control measures, and public health investigations and interventions in relation to this outbreak are described. Treatment recommendations for resource-limited settings are discussed by review of the latest literature.