AbstractThe impact and frequency of infectious disease outbreaks demonstrate the need for timely genomic surveillance to inform public health responses. In the largest known outbreak of mpox, genomic surveillance efforts have primarily focused on high‐incidence nations in Europe and the Americas, with a paucity of data from South‐East Asia and the Western Pacific. Here we analyzed 102 monkeypox virus (MPXV) genomes sampled from 56 individuals in Melbourne, Australia. All genomes fell within the 2022 MPXV outbreak lineage (B.1), with likely onward local transmission detected. We observed within‐host diversity and instances of co‐infection, and highlight further examples of structural variation and apolipoprotein B editing complex‐driven micro‐evolution in the current MPXV outbreak. Updating our understanding of MPXV emergence and diversification will inform public health measures and enable monitoring of the virus’ evolutionary trajectory throughout the mpox outbreak.