The treatment of childhood tuberculosis can be challenging due to the lack of pediatric drug formulations and monitoring of drug-toxicity in routine settings. There are no published studies from Uzbekistan on the adverse drug reactions (ADR) associated with anti-tuberculosis treatment in children. In this study, we aimed to investigate the ADR associated with anti-tuberculosis treatment in children. This was a cohort study using secondary program data of children treated at the city and regional tuberculosis clinics in Tashkent, Uzbekistan. Of the 302 patients evaluated, 135 (44.7%) reported ADR. New tuberculosis was registered in 277 (92%) patients and 262 (87%) had extrapulmonary tuberculosis. Factors associated with ADR included treatment at a regional hospital (adjusted odds ratio, aOR = 1.75; p = 0.026), female sex (aOR = 2.2; p = 0.004), and treatment with second-line drugs (aOR = 8.82; p < 0.001). The most common ADRs were gastrointestinal disorders (28.5%) followed by hepatitis (8.9%) and dermatologic reactions (8.6%). Most of the ADRs were mild (55.6%) or moderate (43.7%), only one child had severe ADR. Patients with the identified risk factors should be closely monitored during the treatment. We also recommend expansion of ADR surveillance throughout the country for more representative data in the future.