(1) Patients on chronic hemodialysis (HD) experience impaired quality of life (QoL). We analyzed HD’s relationship with physical performance, body composition, and muscle strength; (2) QoL was assessed with the Short Form-36, composed of physical (PCS) and mental (MCS) health dimensions. Physical performance was assessed with the Short Physical Performance Battery (SPPB), body composition (lean tissue mass% (LTM%), fat tissue mass% (FTM%), and skeletal muscle mass% (SMM%)) was assessed with bioelectrical impedance, and lower extremity strength was assessed with a handheld dynamometer; and (3) we enrolled 76 patients (27 F, 49 M), age 62.26 ± 12.81 years, HD vintage 28.45 (8.65–77.49) months. Their QoL score was 53.57 (41.07–70.64); their PCS and MCS scores were 52.14 (38.69–65.95) and 63.39 (44.64–76.79) and strongly correlated (p < 0.0001, R = 0.738). QoL correlated positively with SPPB (R = 0.35, p ≤ 0.001), muscle strength (R from 0.21 to 0.41, p < 0.05), and LTM% (R = 0.38, p < 0.001) and negatively with FTM% (R = −0.32, p = 0.006). PCS correlated positively with SPPB (R = 0.42 p < 0.001), muscle strength (R 0.25–0.44, p < 0.05), and LTM% (R = 0.32, p = 0.006) and negatively with FTM% (R = −0.25, p = 0.031). MCS correlated positively with SPPB (R = 0.23, p = 0.047), SMM% (R = 0.25; p = 0.003), and LTM% (R = 0.39, p < 0.001) and negatively with FTM% (R = −0.34; p = 0.003). QoL was unrelated to sex (p = 0.213), age (p = 0.157), HD vintage (p = 0.156), and BMI (p = 0.202); (4) Better physical performance, leaner body composition, and higher muscle strength are associated with better mental and physical QoL in HD.