In September 2023, an ongoing mpox outbreak emerged in South Kivu (Democratic Republic of the Congo) that spread to other regions and countries. Here we describe the epidemiological and genomic evolution of the outbreak between September 2023 and June 2024. Samples were collected from hospitalized patients, along with data on residence and possible exposures. Employee numbers and locations were recorded for bars with sex workers. Where possible, exposures were linked to genomic sequencing data for cluster analysis. In total, 670 cases were admitted to Kamituga General Referral Hospital from 17 health areas. Among the cases, 52.4% were in females and 47.6% in males. The majority (83.4%) were linked to professional sexual interactions. Seven deaths occurred, and three healthcare workers acquired mpox. Eight out of 14 pregnant women had fetal loss. Phylogenetic analysis revealed three clade Ib clusters. Longer branches of a sequence clustering with sequences from Kenya, Uganda, Sweden and Thailand indicate more undocumented spread. Mutations were mostly APOBEC3-type mutations indicative of sustained human-to-human transmission. No clear link between sequence cluster, bar or health area was observed. These data suggest rapid spread mostly through sexual contact within densely populated areas. The spread to neighboring countries highlights the need for extended cross-border collaboration, health education strategies focusing on sex workers, contact tracing, clinical care and surveillance.