Objective: Synovitis is a feature of knee osteoarthritis (OA) and meniscal tear and has been associated with articular cartilage damage. This study was undertaken to examine the associations of baseline effusion-synovitis and changes in effusion-synovitis with changes in cartilage damage in a cohort with OA and meniscal tear. Methods: We analyzed data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial of surgery versus physical therapy for treatment of meniscal tear. We performed semiquantitative grading of effusion-synovitis and cartilage damage on magnetic resonance imaging, and dichotomized effusion-synovitis as none/small (minimal) and medium/large (extensive). We assessed the association of baseline effusion-synovitis and changes in effusion-synovitis with changes in cartilage damage size and depth over 18 months, using Poisson regression models. Analyses were adjusted for patient demographic characteristics, treatment, and baseline cartilage damage. Results: We analyzed 221 participants. Over 18 months, effusion-synovitis was persistently minimal in 45.3% and persistently extensive in 21.3% of the patients. The remaining 33.5% of the patients had minimal synovitis on one occasion and extensive synovitis on the other. In adjusted analyses, patients with extensive effusion-synovitis at baseline had a relative risk (RR) of progression of cartilage damage depth of 1.7 (95% confidence interval [95% CI] 1.0–2.7). Compared to those with persistently minimal effusion-synovitis, those with persistently extensive effusion-synovitis had a significantly increased risk of progression of cartilage damage depth (RR 2.0 [95% CI 1.1–3.4]). Conclusion: Our findings indicate that the presence of extensive effusion-synovitis is associated with subsequent progression of cartilage damage over 18 months. The persistence of extensive effusion-synovitis over time is associated with the greatest risk of concurrent cartilage damage progression.