An outbreak of over 1,000 COVID-19 cases in Provincetown, Massachusetts (MA), in July 2021—the first large outbreak mostly in vaccinated individuals in the US—prompted a comprehensive public health response, motivating changes to national masking recommendations and raising questions about infection and transmission among vaccinated individuals. To address these questions, we combined viral genomic and epidemiological data from 467 individuals, including 40% of outbreak-associated cases. The Delta variant accounted for 99% of cases in this dataset; it was introduced from at least 40 sources, but 83% of cases derived from a single source, likely through transmission across multiple settings over a short time rather than a single event. Genomic and epidemiological data supported multiple transmissions of Delta from and between fully vaccinated individuals. However, despite its magnitude, the outbreak had limited onward impact in MA and the US overall, likely due to high vaccination rates and a robust public health response. Display omitted •Large Delta outbreak in a highly vaccinated population changed US indoor masking policy•Outbreak included multiple Delta introductions; one introduction led to 83% of cases•Spread from and between vaccinated cases contributed, a picture resolved by genomic data•Outbreak was successfully contained; it did not drive the rise of Delta in MA or the US Rapid integration of epidemiological and genomic data was used to support the public health response during a large outbreak of the SARS-CoV-2 Delta variant. The outbreak stemmed primarily from a single source spreading the virus at multiple locations, and while numerous likely transmissions from and between vaccinated individuals were observed, the downstream impact of the outbreak was minimized with robust intervention and community engagement.