Aims: To investigate inflammatory mediator levels in TMJ synovial fluid (SF) and blood and to investigate clinical TMJ symptoms in relation to general and TMJ symptom duration in patients with rheumatoid arthritis (RA). Methods: Examination of 80 TMJs (68 patients; median age 55 years; 85% women) included the following variables: TMJ pain at rest, maximum mouth opening, and palpation; jaw movement capacity; number of painful movements; crepitus; and degree of anterior open bite. Levels of tumor necrosis factor (TNF), TNF soluble receptor II, interleukin 1β, IL-1 receptor antagonist, IL-1 soluble receptor II, and serotonin in TMJ SF and blood; systemic disease activity; and duration of general and TMJ symptoms were assessed. General symptom duration ≤ 2 years was considered early RA. Results: TMJ symptoms predominantly developed within 5 years following general symptom onset. Logistic regression analysis showed that number of involved joints, general pain, maximum mouth opening, anterior open bite, and TNF plasma levels combined explained 46% of the distinction between early and established RA. Furthermore, TMJ pain at rest and maximum mouth opening, contralateral laterotrusion, painful movements, crepitus, and SF TNF levels combined explained 35% of the distinction. In these analyses, higher general pain and maximum mouth opening, TMJ pain on maximum mouth opening, and crepitus were associated with early RA. Conclusion: This study indicates that TMJ pain and crepitus in RA usually occur within 2 years following general symptom onset. Pain-related dysfunction and structural changes develop with time. TNF in plasma and TMJ SF are associated with this development. This makes early (clinical) recognition of pain and inflammation important, enabling early treatment to minimize later irreversible damage.