Purpose: Hypertension is a major risk factor for cardiovascular diseases and stroke, and it requires lifelong medication. This study aimed to investigate the factors impacting on Health-Related Quality of Life (HRQoL) among hypertensive patients in Chongqing, China, and to provide evidence-based strategies to improve their HRQoL. Methods: This cross-sectional survey was conducted in Chongqing, China. Of 600 randomly selected patients, 586 patients agreed to participate and 567 patients completed the survey. A SF-36 (Medical Outcomes Study (MOS) Short Form Health Survey questionnaire) that included eight domains: physical functioning, role limitations due to physical problems, body pain, general health, vitality, social function, role limitations due to emotional problems, and mental health was used to measure HRQoL. Linear regressions were used; each domain of HRQoL was measured in the stratification of sex. Results: Self-perceived relatively low economic burden caused by hypertension and regular physical activity had a positive impact on HRQoL (p < 0.05) for both men and women. For women, younger age was associated with higher scores of measuring physical functioning and body pain. Living with more than three family members had a positive impact on domains, including physical functioning. Emotional self-regulation had a positive association with women’s mental health. Alcohol use for men was associated with higher scores in physical and mental health measures, and emotional self-regulation showed some positive impact on general health. Conclusion: Perceived economic burden caused by hypertension was the most common factor impacting on patients’ HRQoL. Female patients were more susceptible when compared to male patients. Health intervention strategies need to be further explored and adapted to the context of improving HRQoL for patients who suffer from hypertension and other chronic non-communicable diseases.