BACKGROUND: Chronic liver disease (CLD) remains a significant global health concern, with fluctuating mortality trends over the past two decades. This study analyzes age-adjusted CLD mortality rates using data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) from 1999 to 2023, highlighting temporal trends and demographic disparities. METHODS: We conducted a retrospective analysis of CLD mortality rates stratified by year, gender, race, age group, and Hispanicity. Age-adjusted mortality rates were computed using direct standardization, and trends were examined over different periods. RESULTS: Between 1999 and 2006, CLD mortality rates declined from 9.6 to 8.8 per 100,000 population. However, from 2007 onward, mortality rates increased, peaking at 14.5 in 2021, largely driven by the COVID-19 pandemic. Males exhibited consistently higher mortality rates than females. Racial disparities were evident, with American Indian/Alaska Native populations experiencing the highest mortality rates. Age-related trends showed the greatest burden in older adults, while mortality rates in younger populations also rose in recent years. Hispanic individuals demonstrated a significant increase in CLD mortality, particularly post-2010. CONCLUSION: CLD mortality has risen significantly since 2007, with a pronounced peak in 2021. Despite a post-pandemic decline, rates remain above pre-2019 levels. These findings emphasize the significance of customized public health interventions and strategies tackling alcohol use, various metabolic risk factors, and healthcare access, especially for high-risk individuals and populations.