Objective: This study aimed to compare the effectiveness of cervical thrust manipulation and exercise in patients with mechanical neck pain (MNP). Method: Sixty (mean age 31.45 ± 7.31 years) patients were randomized into three groups: manipulation (Group 1); exercise (Group 2); and manipulation plus exercise (Group 3). All interventions were performed 2 days a week for 6 weeks. The visual analog scale (VAS) and Neck Disability Index (NDI) were primary outcome measures; pressure pain threshold (PPT), range of motion (ROM), Short form-36 (SF-36), and Global Rating of Change (GROC) were secondary outcome measures. Results: All parameters improved in all groups (p < .05). Only the minimal clinically important difference (MCID) for NDI was achieved in Group 3. Group 3 had greater improvement in: VAS-rest (p = .004); NDI (p < .001); PPT-left (p = .012); and vitality (p = .002), as well as higher GROC compared to the other groups (p = .043). Group 3 was superior to Group 2 in terms of: ROM (Lateral flexion [LF]-right, p = .003/left, p = .003, rotation-right, p = .012/left, p = .010), PPT-right (p = .022); and emotional well-being (p = .003). Group 1 was superior to Group 2 in terms of ROM (LF-left, p = .043/rotation-left, p = .049). The between-group effect sizes were large (0.12-0.36). Conclusion: The combined application of cervical thrust manipulation and exercise in MNP resulted in greater improvement in clinical parameters, especially function, and higher patient satisfaction in the short term compared to their application alone. Because of its positive effects, cervical thrust manipulation can be added to the exercise program according to the patient's needs and suitability for manipulation.