OBJECTIVE Respiratory syncytial virus (RSV) mortality estimates have not been updated since 2009, and no study has assessed changes in influenza mortality after the 2009 pandemic. Updated burden estimates are needed to characterize long-term changes in the epidemiology of these viruses. OBJECTIVE To evaluate excess mortality from RSV and influenza in the US from 1999 to 2018. METHODS This cross-sectional study used data from 50.3 million US death certificates from 1999 to 2018 to create age-specific linear regression models and assess weekly mortality fluctuations above a seasonal baseline associated with RSV and influenza. Statistical analysis was performed for 1043 weeks from January 3, 1999, to December 29, 2018. METHODS Excess mortality associated with RSV and influenza estimated from the difference between observed and expected underlying respiratory mortality each season. RESULTS There were 50.3 million death certificates (50.1% women and 49.9% men; mean [SD] age at death, 72.7 [18.6] years) included in this analysis, 1.0% for children younger than 1 year and 73.4% for adults aged 65 years or older. A mean of 6549 (95% CI, 6140-6958) underlying respiratory deaths were associated with RSV annually, including 96 (95% CI, 92-99) deaths among children younger than 1 year. For influenza, there were 10 171 (95% CI, 9652-10 691) underlying respiratory deaths per year, with 23 deaths (95% CI, 19-27) among children younger than 1 year. The highest mean mortality rate per 100 000 population for both viruses was among adults aged 65 years or older at 14.7 (95% CI, 13.8-15.5) for RSV and 20.5 (95% CI, 19.4-21.5) for influenza. A lower proportion of influenza deaths occurred among those aged 65 years or older compared with earlier estimates (75.1% [95% CI, 67.4%-82.8%]). Influenza mortality was highest among those aged 65 years or older in seasons when A/H3N2 predominated (18 739 [95% CI, 16 616-21 336] deaths in 2017-2018) and among those aged 5 to 49 years when A/H1N1pdm2009 predominated (1683 [95% CI, 1583-1787] deaths in 2013-2014). Results were sensitive to the choice of mortality outcome and method, with the broadest outcome associated with annual means of 23 352 (95% CI, 21 814-24 891) excess deaths for RSV and 27 171 (95% CI, 25 142-29 199) for influenza. CONCLUSIONS This study suggests that RSV poses a greater risk than influenza to infants, while both are associated with substantial mortality among elderly individuals. Influenza has large interannual variability, affecting different age groups depending on the circulating virus. The emergence of the influenza A/H1N1pdm2009 pandemic virus in 2009 shifted mortality toward middle-aged adults, a trend still observed to date. This study's estimates provide a benchmark to evaluate the mortality benefits associated with interventions against respiratory viruses, including new or improved immunization strategies.