Background Hyperlipidemia is a major cardiovascular disease (CVD) risk factor, but limited data on its mortality trends in CVD over time. We assessed annual hyperlipidemia‐related CVD mortality trends in the United States, including the COVID‐19 pandemic's impact. Methods and Results Mortality data were obtained from CDC repository between 1999 and 2020 among patients ≥15 years old, using ICD‐10 codes hyperlipidemia (E78.0‐E78.5) and CVD (I00‐I99). Age‐adjusted mortality rates (AAMR) per 1,000,000 population was standardized to the 2000 US population. Log‐linear regression models were used to evaluate mortality shifts. Average annual percentage change (AAPC) from 1999‐2019 was used to project 2020 AAMR, estimating pandemic‐attributed excess deaths. From 1999 to 2020, 483,155 hyperlipidemia‐related CVD deaths occurred. Despite a general CVD mortality decline, hyperlipidemia‐related CVD AAMR rose from 36.33 in 1999 to 99.77 in 2019. Ischemic heart diseases (AAMR 49.39) were the leading cause while hypertension had the highest mortality increase (AAPC +10.23%). Mortality rates were higher in males (AAMR 104.87), non‐Hispanic (AAMR 82.49), and rural populations (AAMR 89.98). Highest mortality was observed in Black populations (AAMR 84.35), those ≥75 years (AAMR 646.45), and Western US regions (AAMR 96.88). During the first pandemic year, deaths exceeded projections by 10.55%, with notable increases among ages 35‐75 (14.23%), Hispanic (17.96%), Black (14.82%), and urban (11.68%) groups. Conclusions Hyperlipidemia‐related CVD mortality has risen over the past two decades, further heightened by the COVID‐19 pandemic, with higher impact on males, Black Americans, the elderly, and rural residents. Further study is needed to understand contributing factors and mitigate disparities.