Osteoarthritis (OA) is a common joint disease characterized by progressive joint degeneration and pain. Despite the high prevalence and morbidity of OA, effective treatments are limited. This study identifies Naᵥ1.7 as a voltage-gated sodium channel expressed in chondrocytes, the cells responsible for cartilage degradation in OA. Naᵥ1.7 is upregulated in OA cartilage and is involved in OA progression and pain. Genetic deletion of Naᵥ1.7 in chondrocytes reduces cartilage loss and pain, while deletion in dorsal root ganglia neurons is involved in pain signaling. Pharmacological blockade of Naᵥ1.7 with selective or clinically used pan-Naᵥ channel blockers significantly ameliorates structural joint damage and reduces OA pain. Mechanistically, Naᵥ1.7 blockade regulates intracellular Ca²⁺ signaling and the chondrocyte secretome, which affects chondrocyte biology and OA progression. These findings identify Naᵥ1.7 as a novel therapeutic target for OA, offering both disease-modifying and non-opioid pain relief.Osteoarthritis (OA) is a common joint disease characterized by progressive joint degeneration and pain. Despite the high prevalence and morbidity of OA, effective treatments are limited. This study identifies Naᵥ1.7 as a voltage-gated sodium channel expressed in chondrocytes, the cells responsible for cartilage degradation in OA. Naᵥ1.7 is upregulated in OA cartilage and is involved in OA progression and pain. Genetic deletion of Naᵥ1.7 in chondrocytes reduces cartilage loss and pain, while deletion in dorsal root ganglia neurons is involved in pain signaling. Pharmacological blockade of Naᵥ1.7 with selective or clinically used pan-Naᵥ channel blockers significantly ameliorates structural joint damage and reduces OA pain. Mechanistically, Naᵥ1.7 blockade regulates intracellular Ca²⁺ signaling and the chondrocyte secretome, which affects chondrocyte biology and OA progression. These findings identify Naᵥ1.7 as a novel therapeutic target for OA, offering both disease-modifying and non-opioid pain relief.