The effects of the opioid crisis have varied across diverse and socioeconomically defined urban communities, due in part to widening health disparities. The onset of the COVID-19 pandemic has coincided with a spike in drug overdose deaths in the USA. However, the extent to which the impact of the pandemic on overdose deaths has varied across different demographics in urban neighborhoods is unclear. We examine the influence of COVID-19 pandemic on opioid overdose deaths through spatiotemporal analysis techniques. Using Milwaukee County, Wisconsin as a study site, we used georeferenced opioid overdose data to examine the locational and demographic differences in overdose deaths over time (2017–2020). We find that the pandemic significantly increased the monthly overdose deaths. The worst effects were seen in the poor, urban neighborhoods, affecting Black and Hispanic communities. However, more affluent, suburban White communities also experienced a rise in overdose deaths. A better understanding of contributing factors is needed to guide interventions at the local, regional, and national scales.