Osteoarthritis (OA) is a common joint disease with no effective treatments that prevent joint degeneration and reduce pain. This study identifies NaV1.7 as a voltage-gated sodium channel (VGSC) associated with OA, expressed in chondrocytes. Human OA chondrocytes express functional NaV1.7 channels, with a density of 0.1–0.15 channels per μm² and 350–525 channels per cell. Genetic ablation of NaV1.7 in mouse models shows that NaV1.7 in dorsal root ganglia neurons is involved in pain, while NaV1.7 in chondrocytes regulates OA progression. Pharmacological blockade of NaV1.7 with selective or clinically used pan-NaV channel blockers ameliorates structural joint damage and reduces OA pain behavior. Mechanistically, NaV1.7 blockers regulate intracellular Ca²+ signaling and the chondrocyte secretome, affecting chondrocyte biology and OA progression. Identification of NaV1.7 as a novel chondrocyte-expressed, OA-associated channel reveals a dual target for disease-modifying and non-opioid pain relief treatments for OA. OA is a disabling, degenerative disorder characterized by progressive joint failure. OA involves cartilage breakdown and loss of the extracellular matrix essential for joint function. Chondrocytes undergo complex changes, including anabolic and catabolic alterations, and are central to OA progression. Despite its high prevalence, effective disease-modifying treatments are not available, and the molecular mechanisms of OA remain poorly understood. OA is characterized by significant loss of articular cartilage and pain. Specialized peripheral sensory neurons in joint tissues contribute to OA pain. These neurons express unique repertoires of VGSCs. Nine distinct VGSCs (NaV1.1–NaV1.9) are encoded by genes SCN1A–SCN11A. NaV1.7, NaV1.8, and NaV1.9 are of particular interest as pain targets due to their expression in peripheral sensory neurons and roles in action potential initiation and propagation. Modulation of DRG-expressed NaV1.8 can attenuate OA pain. The critical role of NaV1.7 in pain signaling and genetic validation support its role as a therapeutic target for pain. NaV1.7 gain-of-function mutations increase pain sensitivity in some OA patients. A role of NaV1.7 in inflammatory pain is supported by observations in global NaV1.7 and DRG-specific knockout mice. A role of DRG-expressed NaV1.7 in OA pain was supported by reduced OA pain following spinal administration of ProTx II, a NaV1.7-selective antagonist, in the monosodium iodoacetate (MIA)-inducedOsteoarthritis (OA) is a common joint disease with no effective treatments that prevent joint degeneration and reduce pain. This study identifies NaV1.7 as a voltage-gated sodium channel (VGSC) associated with OA, expressed in chondrocytes. Human OA chondrocytes express functional NaV1.7 channels, with a density of 0.1–0.15 channels per μm² and 350–525 channels per cell. Genetic ablation of NaV1.7 in mouse models shows that NaV1.7 in dorsal root ganglia neurons is involved in pain, while NaV1.7 in chondrocytes regulates OA progression. Pharmacological blockade of NaV1.7 with selective or clinically used pan-NaV channel blockers ameliorates structural joint damage and reduces OA pain behavior. Mechanistically, NaV1.7 blockers regulate intracellular Ca²+ signaling and the chondrocyte secretome, affecting chondrocyte biology and OA progression. Identification of NaV1.7 as a novel chondrocyte-expressed, OA-associated channel reveals a dual target for disease-modifying and non-opioid pain relief treatments for OA. OA is a disabling, degenerative disorder characterized by progressive joint failure. OA involves cartilage breakdown and loss of the extracellular matrix essential for joint function. Chondrocytes undergo complex changes, including anabolic and catabolic alterations, and are central to OA progression. Despite its high prevalence, effective disease-modifying treatments are not available, and the molecular mechanisms of OA remain poorly understood. OA is characterized by significant loss of articular cartilage and pain. Specialized peripheral sensory neurons in joint tissues contribute to OA pain. These neurons express unique repertoires of VGSCs. Nine distinct VGSCs (NaV1.1–NaV1.9) are encoded by genes SCN1A–SCN11A. NaV1.7, NaV1.8, and NaV1.9 are of particular interest as pain targets due to their expression in peripheral sensory neurons and roles in action potential initiation and propagation. Modulation of DRG-expressed NaV1.8 can attenuate OA pain. The critical role of NaV1.7 in pain signaling and genetic validation support its role as a therapeutic target for pain. NaV1.7 gain-of-function mutations increase pain sensitivity in some OA patients. A role of NaV1.7 in inflammatory pain is supported by observations in global NaV1.7 and DRG-specific knockout mice. A role of DRG-expressed NaV1.7 in OA pain was supported by reduced OA pain following spinal administration of ProTx II, a NaV1.7-selective antagonist, in the monosodium iodoacetate (MIA)-induced