Objectives. To estimate all-cause excess deaths in Mexico City (MXC) and New York City (NYC) during the COVID-19 pandemic. Methods. We estimated expected deaths among residents of both cities between March 1 and August 29, 2020, using log-linked negative binomial regression and compared these deaths with observed deaths during the same period. We calculated total and age-specific excess deaths and 95% prediction intervals (PIs). Results. There were 259 excess deaths per 100 000 (95% PI = 249, 269) in MXC and 311 (95% PI = 305, 318) in NYC during the study period. The number of excess deaths among individuals 25 to 44 years old was much higher in MXC (77 per 100 000; 95% PI = 69, 80) than in NYC (34 per 100 000; 95% PI = 30, 38). Corresponding estimates among adults 65 years or older were 1263 (95% PI = 1199, 1317) per 100 000 in MXC and 1581 (95% PI = 1549, 1621) per 100 000 in NYC. Conclusions. Overall, excess mortality was higher in NYC than in MXC; however, the excess mortality rate among young adults was higher in MXC. Public Health Implications. Excess all-cause mortality comparisons across populations and age groups may represent a more complete measure of pandemic effects and provide information on mitigation strategies and susceptibility factors. (Am J Public Health. 2021;111(10): 1847-1850. https://doi.org/10.2105/AJPH.2021.306430).