Background/Objectives: The number of patients with cervical spine pain has been increasing in recent years, and some have been diagnosed with chronic cervicocephalic syndrome (CCS). Collagen mesotherapy of the spine is increasingly being used to treat chronic pain syndromes. This retrospective observational study was conducted to evaluate the efficacy and safety of collagen mesotherapy in the course of CCS. Methods: The study included 31 patients (19 women and 12 men; mean age, 45.0 ± 10.1) with chronic CCS (>12 weeks) who underwent cervical spine mesotherapy using injectable collagen. Mesotherapy was performed at weekly intervals, in 5 (in 18 patients) and 6 (in 13 patients) sessions. Patients were assessed using the Visual Analogue Scale (VAS) for cervical spine pain, pain radiating to the occipital region, dizziness, and tinnitus before the start of mesotherapy, one week after its completion, and 3 months later during a follow-up visit. Changes over time were analyzed using the Friedman test for repeated measures and Cochran’s Q test for binary outcomes. Results: Following collagen mesotherapy, cervical pain on the VAS decreased from 7 (IQR 6–8) at baseline to 2 (IQR 1–3) after treatment and remained at 2 (IQR 1–2) after the 3-month follow-up (p < 0.001). The proportion of patients with occipital pain decreased from 100% to 38.7%, dizziness from 83.9% to 38.7%, and tinnitus from 19.4% to 6.5%. No adverse effects related to the therapy were observed. Conclusions: Collagen mesotherapy was associated with improvements in pain and accompanying symptoms in patients with chronic cervicocephalic syndrome, with no treatment-related adverse events observed. Nevertheless, further research in this area is necessary.