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Rubella virus (RV) infection in susceptible women during the first trimester of pregnancy is associated with congenital Rubella syndrome (CRS). In countries where a vaccination program is implemented, active case surveillance is emphasized. This report documents the magnitude of active cases before and after vaccine implementation in Tanzania. A total of 8750 children and adolescents with signs and symptoms of RV infection were tested for Rubella IgM antibodies between 2013 and 2019 using enzyme immunoassay followed by descriptive analysis. The median age of participants was 3.8 (IQR: 2–6.4) years. About half (4867; 55.6%) of the participants were aged 1–5 years. The prevalence of RV active cases was 534 (32.6%, 95% CI: 30.2–34.9) and 219 (3.2%, 95% CI: 2.7–3.6) before and after vaccine implementation, respectively. Before vaccination, the highest prevalence was recorded in Pemba (78.6%) and the lowest was reported in Geita (15.6%), whereas, after vaccination, the prevalence ranged between 0.5% in Iringa and 6.5% in Pemba. Overall, >50% of the regions had a >90% reduction in active cases. The significant reduction in active cases after vaccine implementation in Tanzania underscores the need to sustain high vaccination coverage to prevent active infections and eventually eliminate CRS, which is the main goal of Rubella vaccine implementation.