Measles is a potentially deadly viral infection spread via respiratory droplets from infected individuals. Outbreaks occur when vaccine coverage drops below the threshold of herd, or community, immunity. Using a sequencing-based approach, we report the prospective (January 7, 2025) detection of measles in nucleic acid extracts from 2 wastewater treatment plants in Houston, Texas, with a population of more than 218 000 residents. The sequencing data from 2 samples contained 53 unique reads mapping to 11 different regions of the measles virus genome with a 99.4% match to genotype B3. Importantly, no detections were observed from 821 previous samples from the same city spanning nearly 3 years of monitoring. The findings were confirmed using droplet digital polymerase chain reaction. A concomitant investigation identified 2 unvaccinated measles-positive travelers living within the same sewershed as the wastewater detection event. This work suggests that sequencing-based wastewater analysis is valuable as a comprehensive early detection warning system that facilitates more targeted epidemiological investigation. (Am J Public Health. Published online ahead of print May 8, 2025:e1-e5. https://doi.org/10.2105/AJPH.2025.308146).