(1) Background: This cohort study aimed to evaluate the effect of patients' treatment expectations on pain perception changes following manual therapy cervical manipulations in individuals with chronic mechanical neck pain. (2) Methods: Demographic data were collected by 56 subjects who were asked to fill out the Neck Disability Index (NDI) and the Expectations for Treatment Scale (ETS). All patients received one single cervical manipulation, and pressure pain thresholds (PPTs) were measured before and immediately after the manipulation with a digital algometer. (3) Results: A total of 56 patients participated. Most subjects (62.5%) had high treatment expectations according to the ETS scale. Statistically significant increases in PPTs were noted both locally and in remote areas (p < 0.05), with 37.5-48.2% of participants showing clinically significant changes in pain perception. However, no statistically significant correlation was found between high treatment expectations and increased PPTs (p > 0.05). (4) Conclusions: Although a significant reduction in pain perception was observed, it did not correlate with patients' treatment expectations. Future research for further investigation of this hypothesis by comparing real versus sham treatment and exploring additional mechanisms affecting changes in PPTs after cervical manipulations in this population will contribute to a better understanding of the research question.