Objective: The incidence of osteoarthritis (OA) increases with each passing year. The degeneration of the meniscus and synovium is considered the initial factor of knee osteoarthritis (KOA), but their synergistic mechanism has not been clarified. Methods: In this study, single-cell RNA sequencing (scRNA-seq) was employed to establish 16 normal or degenerated meniscus samples and 6 synovium samples based on the meniscus and synovium tissues of 16 patients. A cell atlas comprising 124,026 single cells in total was established (including 8 patients from the public database The Genome Sequence Archive for Human (GSA-Human) PRJCA008120). Results: Based on the exploration of the meniscus/synovium microenvironment homeostasis and the crosstalk between them during their degeneration, this study provided a comprehensive description of the involved cellular interactions. The cell types present in the meniscus and synovium were analyzed, and new fibroblast subtypes related to their degeneration were identified. Additionally, the interactions within pathways such as vascular endothelial growth factor (VEGF) and VISFATIN between the meniscus and synovium were studied, with a focus on various cell subtypes. The mechanisms involving vascular growth, immune cell infiltration, and common or distinct genes during the degeneration of synovium and meniscus tissues were also investigated. Conclusion: This study presented the largest cellular atlas of the synovium and meniscus in osteoarthritis (OA) to date, reflecting a detailed description of the cellular crosstalk during degeneration. The findings suggested that the synovium played a significant role in the intra-articular tissue crosstalk (synovium/meniscus), thereby contributing to the degeneration observed in OA.