Background. Studies on the long-term treatment outcomes of childhood acute lymphoblastic leukemia (ALL) in resource-limited countries are scarce. The purpose of this study was to assess the evolution of survival outcomes of pediatric ALL in a tertiary care center in Thailand over a 40-year period. Patients and methods. We retrospectively reviewed the medical records of pediatric patients who were diagnosed with ALL and treated at our center between June 1979 and December 2019. We classified the patients into 4 study periods depending on the therapy protocol used to treat the patients (period 1: 1979-1986, period 2: 1987-2005, period 3: 2006-2013, and period 4: 2014-2019). The Kaplan Meier method was used to determine overall and event-free survival for each group. The log-rank test was used to identify statistical differences. Results. Over the study period, 726 patients with ALL were identified, 428 boys (59%) and 298 girls (41%), with a median age at diagnosis of 4.7 years (range: 0.2–15 years). The study periods 1, 2, 3, and 4 had 5-year event-free survival (EFS) rates of 27.6%, 41.6%, 55.9% and 66.4%, and 5-year overall survival (OS) rates of 32.8%, 47.8%, 61.5%, and 69.3%, respectively. From period 1 to period 4, both the EFS and OS rates increased significantly (p<0.0001). Age, study period, and white blood cell (WBC) count were all significant prognostic indicators for survival outcomes. Conclusions. The overall survival of patients with ALL treated in our center improved significantly over time from 32.8% in period 1 to 69.3% in period 4.