Background: Infection with the hepatitis B virus (HBV) poses a serious threat to global public health. More than 300 million instances of chronic hepatitis are brought on by it, which is the primary cause of liver disease. This study was conducted to determine the risk factors of HBV in children at Jinnah Postgraduate Medical Centre, Karachi, Sindh, Pakistan. Materials and methods: This cross-sectional study was conducted at the Department of Gastroenterology, Jinnah Postgraduate Medical Centre, Karachi, Sindh, Pakistan from January 2019 to April 2022. A total of 134 children aged below 16 years with HBV were recruited in this study. Demographic information was recorded. Screening for HBV was done in all patients. Investigations including liver biochemistry, hepatitis B surface antigen (HBsAg), and HBV DNA polymerase chain reaction (PCR) were conducted in the hospital along with a complete blood count and ultrasound whole abdomen. All information was collected on a predesigned proforma and evaluated using statistical package for the social sciences (SPSS), version 25.0, software. Results: The mean age of patients was 11.02 ± 2.19 years. There were 57.46% males. The frequent risk factor was vertical transmission in 47% of children followed by blood transfusion in 23.9% of children, horizontal transmission in 13.4% of children, and prior history of surgical or dental intervention in 17.2% of children. Conclusion: In this study, vertical transmission was the most common route of transmission of HBV. Additionally, 11% of family members were HBV positive. None had concomitant hepatitis C virus (HCV) and HDV infection. All pregnant females should be screened. Children on chronic blood transfusion therapy should be screened annually. Additionally, birth-dose HBV vaccination should be implemented as a key step in HBV prevention among Pakistani children.