To determine the magnitude of increases in monthly drug-related overdose mortality during the COVID-19 pandemic in the United States. We leveraged provisional records from the Centers for Disease Control and Prevention provided as rolling 12-month sums, which are helpful for smoothing, yet may mask pandemic-related spikes in overdose mortality. We cross-referenced these rolling aggregates with previous monthly data to estimate monthly drug-related overdose mortality for January through July 2020. We quantified historical errors stemming from reporting delays and estimated empirically derived 95% prediction intervals (PIs). We found that 9192 (95% PI = 8988, 9397) people died from drug overdose in May 2020-making it the deadliest month on record-representing a 57.7% (95% PI = 54.2%, 61.2%) increase over May 2019. Most states saw large-magnitude increases, with the highest in West Virginia, Kentucky, and Tennessee. We observed low concordance between rolling 12-month aggregates and monthly pandemic-related shocks. Unprecedented increases in overdose mortality occurred during the pandemic, highlighting the value of presenting monthly values alongside smoothed aggregates for detecting shocks. Drastic exacerbations of the US overdose crisis warrant renewed investments in overdose surveillance and prevention during the pandemic response and postpandemic recovery efforts.