Knee osteoarthritis (KOA) is a leading cause of disability, and local data on its impact on quality of life (QoL) remain limited. This study aimed to determine the QoL and its associated factors among patients with KOA. A cross-sectional study was conducted among patients aged 40 years and older with clinically or radiographically confirmed KOA at Hospital Pakar Universiti Sains Malaysia. QoL was assessed using theye validated Malay version of the Osteoarthritis of Knee and Hip Quality of Life (OAKHQoL) questionnaire and the Malay version of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC- VAS scale). Sociodemographic and clinical data were collected. Univariate analysis identified potential predictors of QoL, and multivariable linear regression was used to determine independent predictors. Of the 166 patients recruited, 152 completed the study (response rate 92%). Participants reported substantial pain and disability, reflected by a high mean WOMAC score of 939.7 ± 484.1 (range 49–2042). The most affected domain of the OAKHQoL was social functioning (59.1 ± 26.3). The overall OAKHQoL score was 41.8 ± 16.2, indicating a moderate reduction in QoL. Univariate analysis revealed that higher BMI (p = 0.033), a history of ischemic heart disease (p = 0.040), glucosamine use (p = 0.009), and higher WOMAC scores (p < 0.001) were associated with poorer QoL. Multivariable linear regression identified higher WOMAC scores (β = 0.025, 95% CI: 0.021–0.028, p < 0.001) and KOA grade 3 and 4 (β = 5.06, 95% CI: 0.048–10.06, p = 0.048) as independent predictors. Specifically, one unit increase in WOMAC score corresponded to a 0.025-unit increase in OAKHQoL score, while KL grades 3 and 4 were linked to a 5.06- unit higher OAKHQoL score. These findings highlight the central role of symptom severity and structural damage in shaping QoL in KOA. Early intervention, symptom management, and psychosocial support are essential to improve outcomes