Background: Infections are a major cause of morbidity and mortality among paediatric patients undergoing chemotherapy for acute lymphoblastic leukemia (ALL). This study aims to evaluate the incidence, types, and outcomes of infections in paediatric ALL patients during various chemotherapy phases. Methods: A prospective observational study was conducted on 75 paediatric ALL patients receiving chemotherapy in a tertiary care hospital. Patients were stratified as per National Cancer Institute (NCI) criteria. Data on socio-demographics, risk stratification, chemotherapy phases, infection types, microbiological profiles, and outcomes were collected and analyzed. Data analysis was performed using SPSS version 29. Results: This study had a mean age of 6.16 ± 3.09 years, with a male-to-female ratio of 1.42:1. High-risk patients constituted 52%. Infections occurred in 88% of patients, with bloodstream and respiratory tract infections each accounting for 37.88%. Fever (96.9%) and febrile neutropenia (90.9%) were the most common presentations. Overall mortality was 12%, with septicemia (55.6%) and pneumonia (44.4%) being the leading contributors. Culture-positive infections were found in 36% of cases, predominantly Candida species (13.3%) and Staphylococcus aureus (5.3%). Deceased patients had significantly lower mean total leukocyte count (TLC = 1297.78/µl) and absolute neutrophil count (ANC = 134.44/µl) compared to survivors (p < 0.0001). Conclusion: Infections significantly impact mortality in pediatric ALL patients undergoing chemotherapy, especially among high-risk patients with neutropenia. Early identification and management, along with monitoring hematological parameters, are crucial for improving outcomes.