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Intensive efforts have been made to develop models of hRSV infection or disease using various animals. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we present a mouse model based on a <i>Rag2</i> gene knockout using CRISPR/Cas9 technology. Rag2^−/− mice sustained high viral loads upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1 × 10^9.8 copies/g and 1c10⁶ TCID₅₀ in nasal cavity, as well as 1 × 10⁸ copies/g and 1 × 10⁵ TCID₅₀ in the lungs up to 5 weeks. Mild interstitial pneumonia, severe bronchopneumonia, elevated cytokines and NK cells were seen in Rag2^−/− mice. A humanized monoclonal antibody showed strong antiviral activity in this animal model, implying that Rag2^−/− mice that support long-term stable infection are a useful tool for studying the transmission and pathogenesis of human RSV, as well as evaluating therapeutics.