Objective: To compare the effects of dry needling and upper cervical spinal manipulation with interocclusal splint therapy, diclofenac, and temporomandibular joint (TMJ) mobilization in patients with temporomandibular disorder (TMD). Methods: One hundred-twenty patients with TMD were randomized to receive six treatment sessions of dry needling plus upper cervical spinal manipulation (n = 62) or interocclusal splint therapy, diclofenac, and joint mobilization to the TMJ (n = 58). Results: Patients receiving dry needling and upper cervical spinal manipulation experienced significantly greater reductions in jaw pain intensity over the last 7 days (VAS: F = 23.696; p < 0.001) and active pain-free mouth opening (F = 29.902; p < 0.001) than those receiving interocclusal splint therapy, diclofenac, and TMJ mobilization at the 3-month follow-up. Conclusion: Dry needling and upper cervical spinal manipulation was more effective than interocclusal splint therapy, diclofenac, and TMJ mobilization in patients with TMD.