Background/Objectives: Chronic hepatitis C virus (HCV) remains a major public health concern in Taiwan, particularly in southern regions with high endemicity. While HCV elimination is a national priority, resources are often limited. Relying solely on broad, township-level prevalence rates is inefficient, as the true disease burden can vary dramatically at the village level. Therefore, identifying local hotspots through fine-scale mapping is critical for efficient resource allocation and targeted intervention. This study aimed to validate village-level prevalence estimates and evaluate the efficiency of a community-based, targeted screening approach utilizing this detailed prevalence data in Chiayi County. Methods: We integrated data from the Chiayi Health Bureau and Chiayi Chang Gung Memorial Hospital (2000–2015) to generate village-level risk maps for five townships: Lioujiao (LJ), Yijhu (YH), Dongshih (DS), Taibao (TB), and Lucao (LC). Between 2018 and 2021, we conducted door-to-door community screening using anti-HCV testing with reflex HCV antigen (Ag) testing. Anti-HCV/HCV Ag prevalence, number needed to test (NNT), and linkage-to-care rates were calculated to validate prevalence estimates and assess screening efficiency. Results: Among 3910 participants, anti-HCV prevalence ranged from 5.4% (TB) to 8.7% (DS). Estimated and observed village-level prevalence showed moderate-to-strong correlation (r = 0.696–0.830, p < 0.001). Screening efficiency was highest in DS (NNT = 21) and lowest in TB (NNT = 42). Of 132 antigen-positive individuals, 131 (99.2%) initiated direct-acting antiviral therapy. Conclusions: The village-level risk maps accurately predicted local HCV burden, enabling targeted screening with high diagnostic yield and near-complete treatment uptake. This approach maximizes resource efficiency and may serve as a scalable model for advancing Taiwan and the WHO’s 2030 HCV elimination goals.