The objective of the present study was to determine the association between lifestyle parameters (i.e., physical activity (PA) level, screen time (ST), fitness and food habits) and health-related quality of life (HRQoL) in ethnic ascendant schoolchildren (i.e., Mapuche ascendant). This cross-sectional study included 619 schoolchildren with ethnic (EA; n = 234, 11.6 ± 1.0 years) and non-ethnicity ascendant (NEA; n = 383, 11.7 ± 1.1 years) from Araucanía, Chile. HRQoL and lifestyle were measured using a standard questionnaire and cardiometabolic markers (body mass index (BMI), waist circumference (WC), waist-to-height ratio (WtHR), systolic (SBP) and diastolic blood pressure (DBP)) and cardiorespiratory fitness (CRF) were additionally included. In the EA schoolchildren, the HRQoL reported association with CRF adjusted by age and sex (β; 0.12, p = 0.018) and non-adjusted with foods habits (β; 0.11, p = 0.034). By contrast, ST adjusted by age and sex presented an inverse association with HRQoL (β; −2.70, p < 0.001). EA schoolchildren showed low HRQoL (p = 0.002), low nutritional level (p = 0.002) and low CRF (p < 0.001) than NEA peers. Moreover, children’s ethnic presence showed an association with low nutritional levels (odd ratio (OR): 3.28, p = 0.002) and ST 5 h/day (OR: 5.34, p = 0.003). In conclusion, in the present study, EA schoolchildren reported lower HRQoL than NEA schoolchildren, which could be explained by the lifestyle patterns such as a low nutritional level and more ST exposure.