This study aimed to verify the prevalence and characteristics of sports injuries (SI) and determine the association between the physical activity level (PA) and SI with perception of health-related quality of life (HRQoL) in Brazilian basketball master athletes. A cross-sectional study was conducted with 410 male master athletes, between 35 and 85years of age (mean 52.26, SD +/- 11.83). The HRQoL was assessed using the Medical Outcomes Study - Short Form-36. The PA was evaluated using the International Physical Activity Questionnaire. Information regarding SI was collected using the Reported Morbidity Survey. Poisson regression, as estimated by the prevalence ratio (PR), was used as a measure of the association of PA and SI with HRQoL. The majority of athletes showed a high SI prevalence (58.3%) and reported one injury (67.8%) that occurred during training (61.1%) and primarily affected a lower limb (74.6%). The adjusted regression models showed a positive association of PA with the Functional Capacity (PR=1.46, 95% confidence interval [CI]=1.12-1.90) and Physical Component (PR=1.32, 95% CI=1.03-1.70) of HRQoL. Furthermore, the SI were negatively associated with HRQoL in Functional Capacity (PR=1.85, 95% CI=1.51-2.27), Physical Aspects (PR=3.99, 95% CI=3.08-5.18), Pain (PR=1.65, 95% CI=1.26-2.16), Social Functioning (PR=1.79, 95% CI=1.41-2.27), Emotional Aspects (PR=4.40, 95% CI=3.35-5.78), Mental Health domains (PR=1.37, 95% CI=1.06-1.68), Physical Component (PR=2.35, 95% CI=1.90-2.90) and Mental Component (PR=2.65, 95% CI=2.14-3.29). These results highlighted that master athletes showed a high SI prevalence, primarily in the lower limbs. PA positively correlates with the physical HRQoL domain, whereas SI may decrease the HRQoL levels of both physical and mental domains.