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Simple Summary: Worldwide, prostate cancer (PC) causes high morbidity and mortality. Thus, developing effective strategies for the prevention, diagnosis, and control of this disease is fundamental to providing updated and reliable estimations of the PC burden both nationally and subnationally. Herein, we analyzed data from the Global Burden of Disease study to estimate PC incidence and mortality, and their trends in Mexico at the national and subnational levels from 2000 to 2019. Our results show that PC was the top ranked cause of death among malign neoplasms in males from Mexico during 2019. Males from 70 to 79 years of age were the most affected by PC, and there was an increasing trend in the burden of this cancer. There was substantial subnational heterogeneity that suggested differential geographical patterns of change. These results provide both comprehensive and comparable estimates to assist the effort to reduce health loss due to PC. In 2019, the Global Burden of Disease (GBD) estimated that prostate cancer (PC) was the 16th most common cause of death globally in males. In Mexico, PC epidemiology has been studied by a number of metrics and over various periods, although without including the most up-to-date estimates. Herein, we describe and compare the burdens and trends of PC in Mexico and its 32 states from 2000 to 2019. For this study, we extracted online available data from the GBD 2019 to estimate the crude and age-standardized rates (ASR per 100,000 people) of the incidence and mortality of PC. In Mexico, PC caused 27.1 thousand (95% uncertainty intervals, 20.6–36.0 thousand) incident cases and 9.2 thousand (7.7–12.7 thousand) deaths in males of all ages in 2019. Among the states, Sinaloa had the greatest ASR of incidence, and Guerrero had the highest mortality. The burden of PC showed an increasing trend, although the magnitude of change differed between metrics and locations. We found both an increasing national trend and subnational variation in the burden of PC. Our results confirm the need for updated and timely estimates to design effective diagnostic and treatment campaigns in locations where the burden of PC is the highest. [ABSTRACT FROM AUTHOR]