Purpose: To compare the effectiveness of a single exercise session with manual therapy techniques in the segments of the upper cervical spine (C0–1, C1–2 and C2–3), against a single exercise session in patients with chronic neck pain and mobility deficits in the upper cervical spine. Methods: A single-blind randomized controlled trial was performed. Fifty-eight patients were recruited (29 for the manual therapy and exercise group and 29 for the exercise group) who presented chronic neck pain and upper cervical spine dysfunction. The exercise focused on the deep muscles. The manual therapy combined manipulations and mobilizations with these exercises. Cervical range of motion, flexion-rotation test, pressure pain threshold and pain intensity were measured by a blind evaluator before and after the intervention. Results: Compared to pre-intervention, after intervention, the exercise group was significantly lower in terms of the range of motion, flexion-rotation test, and pressure pain threshold (p < 0.05). The manual therapy and exercise group improved in upper cervical flexion, the flexion-rotation test and intensity of pain (p < 0.05). Conclusions: It may be necessary to normalize the mobility of the upper cervical spine before cervical stabilization training, in patients with chronic neck pain and mobility deficits in the upper cervical spine.