Health-related quality of life (HRQoL) reflects an individual's perception of their physical and mental health over time. Despite numerous studies linking physical activity to improved HRQoL, most rely on self-reported data, limiting the accuracy and generalizability of findings. This study leverages objective accelerometer data to explore the association between physical activity and HRQoL in Korean adults. The objective of this study is to analyze the relationship between objectively measured physical activity using accelerometers and HRQoL among Korean adults, aiming to inform targeted interventions for enhancing HRQoL through physical activity. This observational study included 1298 participants aged 19-64 years from the Korea National Health and Nutrition Examination Survey (KNHANES) VI, who wore an accelerometer for 7 consecutive days. HRQoL was assessed using the EQ-5D questionnaire, and physical activity was quantified as moderate-to-vigorous physical activity accelerometer-total (MVPA-AT) and accelerometer-bout (MVPA-AB). Data were analyzed using logistic regression to determine the odds ratio (ORs) for low HRQoL, adjusting for socioeconomic variables and mental health factors. Participants with higher HRQoL were younger, more likely to be male, single, highly educated, employed in white-collar jobs, and had higher household incomes. They also reported less stress and better subjective health status. The high HRQoL group had significantly more participants meeting MVPA-AB ≥600 metabolic equivalents (P<.01). Logistic regression showed that participants meeting MVPA-AB ≥600 metabolic equivalents had higher odds of high HRQoL (OR 1.55, 95% CI 1.11-2.17). Adjusted models showed consistent results, although the association weakened when adjusting for mental health factors (OR 1.45, 95% CI 1.01-2.09). The study demonstrates a significant association between HRQoL and moderate to vigorous physical activity sustained for at least 10 minutes, as measured by accelerometer. These findings support promoting physical activity, particularly sustained moderate to vigorous activity, to enhance HRQoL. Further interventional studies focusing on specific physical activity domains such as occupational, leisure-time, and commuting activities are warranted.