Physical activity can help improve the poor health-related quality of life in older adult population. Although the Physical Activity Guidelines for Americans recommend both aerobic and muscle strengthening activities for adults, previous studies predominantly focused on aerobic activity with limited research on muscle strengthening activities. The purpose of this cross-sectional study was to examine the relationships between meeting physical activity guidelines (i.e., aerobic activity, muscle strengthening activity) and health-related quality of life in the older adult population. Data of 87,495 older adults aged ≥65 years from the U.S. 2019 Behavioral Risk Factor Surveillance System were analyzed. Phone interviews and validated questionnaires were used to assess aerobic activity, muscle strengthening activity, and health-related quality of life. Binomial logistic regression was used to examine the relationships between meeting physical activity guidelines and health-related quality of life while adjusting for key covariates (i.e., age, sex, race, education, marital status, employment status, income, body mass index, smoking, drinking, and comorbidities). Participants meeting both or aerobic activity guideline only had significantly lower odds of reporting all components of health-related quality of life (i.e., general health, mental health, physical health, activity limitation) than those who met neither guideline (OR = 0.37-0.58) and those who met muscle strengthening activity guideline only (OR = 0.34 - 0.74). Given the stronger positive association between aerobic activity and health-related quality of life than that between muscle strengthening activity and health-related quality of life, future research should focus on promoting aerobic activity to increase health-related quality of life among older people. •Meeting both physical activity guidelines was related to better health-related quality of life in older adults.•Meeting aerobic activity guideline only was associated with better health-related quality of life in older adults•Meeting muscle strengthening activity guideline only was associated with better general and mental health.•Meeting aerobic activity guideline contributes to the most benefits of physical activity on health-related quality of life.