In Pakistan, Major depressive disorder (MDD) contributes significantly to the mental health burden. It is crucial to understand patients' medication adherence status for developing a strategy for improving adherence and treatment outcomes. Therefore, a valid and reliable tool in the local Urdu language is required. The Morisky, Greene, and Levine Medication Adherence Scale (MGLS-4) is a reliable, valid and straightforward instrument to assess medication-taking behavior. The valid and reliable Urdu translation of MGLS-4 can fill this gap within the local context. Therefore, the present study aims to validate the Urdu Morisky, Green and Levine Adherence Scale (UMGLS-4) for MDD patients. This was a quantitative, cross-sectional validation study for Pakistani MDD patients. Reliability was measured using Cronbach's α and for test-retest reliability intraclass correlation coefficient (ICC) was calculated. Validity was assessed through face validity, content validity, construct validity, and convergent validity with the Drug Attitude Inventory (DAI-10). Descriptive and inferential statistical analyses were carried out to demonstrate adherence level and statistical significance, respectively. Linear regression was applied to find the association between the UGMLS-4 score and demographic characteristics. The UMGLS-4 demonstrated high reliability (Cronbach's α = 0.829) and a significant strong ICC (x = 0.601, p < 0.01) was detected. Exploratory factor analysis (EFA) revealed a single-factor structure explaining 66.084% of the variance. Confirmatory factor analysis (CFA) confirmed good model fit (GFI = 0.950, AGFI = 0.920, NFI = 0.930, RMSEA = 0.050, SRMSR = 0.055). Medication adherence was observed to be high in 39.1% of patients, moderate in 28.6%, and poor in 32.3%. Significant associations were found between adherence scores and gender, educational attainment, and occupational status (p < 0.005) with education predicting adherence (B = 0.301, p < 0.000), indicating the scale's robustness in detecting adherence variations among Urdu-speaking MDD patients. The UMGLS-4 is a reliable and valid tool for assessing medication adherence in Pakistani MDD patients, effectively capturing adherence variations across demographic variables.