The mortality from Parkinson disease (PD) and its long-term trends in the United States in recent decades remains unknown. This study aimed to describe the trends in PD mortality in the United States from 1999 to 2019. We used data from the National Vital Statistics System, a nationwide, population-based death registry, to determine national trends in PD mortality, overall and by age, sex, race/ethnicity, urban-rural classification, and geographic location. Analyses focused on the data from 479,059 deaths due to PD from 1999 to 2019. Joinpoint regression was performed to examine temporal trends in age-adjusted death rates. The age-adjusted mortality from PD increased from 5.4 (95% confidence interval [CI] 5.3-5.5) per 100,000 population in 1999 to 8.8 (95% CI, 8.7-8.9) per 100,000 population in 2019, with an average annual percent change of 2.4% (95% CI, 1.8%-3.0%). From 1999 to 2019, PD mortality increased significantly across all age groups, both sexes, various racial/ethnic groups, and different urban-rural classifications. The US states and District of Columbia with reported death rates all experienced an increase in PD mortality. Significant differences by sex and race/ethnicity were noted. Age-adjusted PD mortality rates were twice as high in men as in women and were greater in White individuals than those from other racial/ethnic groups. From 1999 to 2019, the mortality from PD in the United States has increased significantly. The increase was regardless of age, sex, race/ethnicity, urban-rural classification, and geographic location. A comprehensive evaluation of long-term trends in PD mortality is important for health care priority setting.