Background <p>Hypertension is a prevalent chronic medical condition that can impact health-related quality of life (HRQoL). While a relationship between mental disorders and hypertension is established, the incremental impact of co-occurring mental disorders on HRQoL in hypertensive individuals has not been well-quantified. This study’s primary objective is to examine this relationship using a nationally representative sample.</p> Methods <p>A retrospective cross-sectional study design was employed. This research uses data from 2016 to 2021 from the Medical Expenditure Panel Survey (MEPS). The study included adult patients with hypertension diagnosis who were 18 years of age or older. The Veterans RAND 12 Item Health Survey (VR-12©) was used to determine HRQoL. A linear regression model was used to estimate the predictors of HRQoL.</p> Results <p>A total of 11,773 adults with hypertension were identified. Among them, 8.0% had depression, 9.8% had anxiety, and 6.1% had both illnesses. Hypertensive patients with anxiety or depression had a significantly lower mean PCS score and MCS score compared to those without these mental illnesses. After adjusting for other variables, the HRQoL of hypertensive patients with depression (MCS: β = -6.398), anxiety (MCS: β = -4.438), and both illnesses (MCS: β = -9.211) was significantly lower than that of individuals without these conditions.</p> Conclusions <p>Depression and anxiety were significantly associated with reduced HRQoL among adults with hypertension. These findings emphasize the significant mental burden in this population. Given the cross-sectional natural of this study, causal relationships could not be established; therefore, future longitudinal studies are needed to explore the direction and mechanisms of these associations.</p>