PURPOSE Acute lymphoblastic leukemia (ALL) represents around 70% of pediatric leukemia. In high-income countries, the 5-year survival is above 90%, but survival in low- and middle-income countries is inferior. This study documents the treatment outcome and prognostic factors of pediatric ALL in Pakistan. MATERIALS AND METHODS In this prospective cohort study, all newly diagnosed patients with ALL/lymphoblastic lymphoma from age 1 to 16 years enrolled between January 1, 2012, and December 31, 2021, were included. The treatment was based on the standard arm of the UKALL2011 protocol. RESULTS Data from 945 patients with ALL, including 597 males (63.2%), were analyzed. The mean age at diagnosis was 5.73 ± 3.51 years. Pallor was the commonest presentation in 95.2% followed by fever in 84.2% of patients. The mean WBC count was 56.6 ± 103.4 × 109/L. Neutropenic fever followed by myopathy was the most common complication during induction. In univariate analysis, the high WBC count ( P ≤ 0.001), intensive chemotherapy ( P ≤ 0.001), malnutrition ( P = .007), poor response to induction chemotherapy ( P = .001), delayed presentation ( P = .004), and use of steroids before chemotherapy ( P = .023) significantly adversely affected overall survival (OS). The delayed presentation was the most significant prognostic factor in the multivariate analysis ( P ≤ .002). After a median follow-up of 54.64 ± 33.80 months, the 5-year OS and disease-free survival (DFS) were 69.9% and 67.8%, respectively. CONCLUSION In this largest cohort of childhood ALL from Pakistan, a high WBC count, malnutrition, delayed presentation, previous steroids use, intensive chemotherapy, and poor response to the induction chemotherapy were associated with decreased OS and DFS rates.