Multiple sclerosis is an inflammatory and neurodegenerative disease that leads to motor, cognitive, and sensory impairments, significantly affecting walking and quality of life. This study aimed to analyze the relationship between quality of life and kinematic walking parameters in individuals with multiple sclerosis, as well as to evaluate the influence of fatigue, balance, and cognitive performance on different aspects of quality of life. A cross-sectional observational study was conducted with 32 patients diagnosed with multiple sclerosis with Expanded Disability Status Scale scores of ≤5.5. Quality of life was assessed using the MusiQoL questionnaire, and clinical variables included fatigue (Fatigue Scale for Motor and Cognitive Functions, Borg scale), balance (Berg Balance Scale), and cognitive performance (Trail Making Test). Walking kinematics were analyzed using the Vicon motion capture system to obtain walking speed, step frequency, and joint asymmetry indices. Spearman correlations and linear regression models were applied. Results showed significant correlations between quality of life and walking speed (rho = 0.506), step frequency (rho = 0.508), and knee asymmetry (rho = −0.525), as well as strong associations with cognitive fatigue (rho = −0.796) and balance (rho = 0.635). Regression models explained up to 58.4% of the variance in the Activities of Daily Living dimension. These findings indicate that quality of life in multiple sclerosis is influenced by both clinical and biomechanical factors, highlighting the importance of comprehensive assessments to guide physiotherapeutic interventions.