BACKGROUND: Oropouche virus (OROV) is an emerging vector-borne pathogen endemic to the Americas, which causes acute febrile illness (AFI) in humans. Starting in late 2023, surges in OROV infections were reported across Latin America, including an outbreak in Iquitos, a city in the Eastern Peruvian Amazon, where RIVERA, an ongoing AFI surveillance program detected and characterized incident OROV cases. METHODS: AFI cases presenting to health facilities were screened for OROV using PCR. OROV-positive subjects were compared to AFI OROV negative cases to describe the principal features of clinical disease. Genomes from OROV strains were sequenced and compared using phylogenetic analysis with those from extant samples isolated from other locations in the Americas. FINDINGS: In early 2024, an 8.6% OROV-positivity rate (29 detections in 339 samples) in RIVERA subjects was recorded, a more than 20-fold increase compared with pre-outbreak levels. Illness was characterized by fever, arthralgia, myalgia and dysuria. Genome sequences from strains in this outbreak were phylogenetically distinct from those from a concurrent one in Brazil, but resembled strains from Colombia and Ecuador. The last common ancestor of outbreak strains from Peru and Brazil was 226 years prior to sampling, and that of Peru and Ecuador and Colombia approximately 10 and 8 years prior to sampling, respectively. INTERPRETATION: Genomic analysis suggests that the current outbreak in South America is multifocal in origin and not the result of geographic spread from Brazil. An existing AFI surveillance program successfully documented the emergence and characterized the symptom profile of this emerging arboviral disease. FUNDING: CDC/HHS U01GH002270; NIH D43TW010913, K43TW012298, K01AI168493, 5T32AI007046-48.