Physical activity (PA) can improve health and quality of life (QOL) of healthy people. However, the association between PA and QOL among people with physical disability (PWPD) is inconclusive. This study was conducted to determine the relationships between factors including intensity of PA, activitiy in daily living (ADL), stress, and self-esteem that influences self-reported QOL among PWPD. The relationships were further explored using the in-depth interview method to find out whether the intensity of PA, stress, and self-esteem are related to QOL perception in PWPD. One hundred sixty PWPD aged 18-48 years who studied at a vocational school were enrolled. A mixed method case study was conducted: cross-sectional survey and in-depth interview. Five questionnaires, including the Barthel Index, Perceived Stress Scale (PSS), Rosenberg Self-Esteem Scale (RSES), and Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) were distributed. QOL was measured using the WHOQOL_BREF. Multiple linear regression was used to determine factors for QOL prediction. For in-depth interview, ten persons from each group (poor-to-fair and good QOL) volunteered to explore further about life satisfaction related to physical disability. One hundred forty-six (91%) subjects completed all questionnaires. One hundred fourteen (77%) reported poor-to-fair QOL. QOL was explained by self-esteem and ADL (adjusted R² 34.7%, p < 0.001) after adjusted for age, stress, and PA. Although PA could not explain QOL in PWPD, good QOL reported high activities (28.40 ± 30.20 MET hour/day) compared to poor and fair QOL (17.94 ± 22.06 and 21.70 ± 17.75 MET hour/day). Those who had good QOL reported that they were proud to be independent and did not feel inferior. PA participation among people with disabilities should therefore be encouraged.