Neck pain is a common musculoskeletal condition frequently managed with numerous conservative interventions. The McKenzie method of mechanical diagnosis and therapy (MMDT) is a form of physical therapy evaluation and treatment that aims to improve pain and disability in patients with musculoskeletal pain, including neck pain. To date, no systematic review with meta-analysis has examined the use of the McKenzie MMDT for neck pain. This study aimed to examine the effectiveness of the McKenzie MMDT in adult patients with neck pain. A systematic review and meta-analysis were performed using PubMed, ScienceDirect, MEDLINE, CINAHL, Web of Science, and Google Scholar. Full search terms were “McKenzie method” OR “McKenzie approach” OR “McKenzie treatment” AND “neck pain.” Inclusion criteria were the use of the McKenzie MMDT, level I randomized control trials (RCTs), adults, and outcomes of pain (0-10 scale) and disability (neck disability index). A total of 11 RCTs met the final selection criteria from 1,955 articles on initial search with 289 patients receiving the McKenzie MMDT out of 677 total patients. For meta-analysis, there was a clinically insignificant but statistically significant improvement in pain (1.14/10 points) in patients receiving the McKenzie MMDT versus control interventions (p<0.02). There was no significant improvement in the neck disability index score between the McKenzie MMDT versus control interventions (p=0.19). For severity of pain, there was a clinically and statistically significant improvement in moderate or severe pain (2.06/10 points; p<0.01), but not in mild-to-moderate pain (p=0.84) when comparing the McKenzie MMDT to control interventions. Overall, the McKenzie MMDT provides very small but statistically significant improvements in neck pain of all severity compared to control interventions. However, the McKenzie MMDT does provide clinically and statistically significant pain improvement in moderate-to-severe neck pain. Use of the McKenzie MMDT did not provide any significant improvement in disability compared to control interventions. This study is the first systematic review with meta-analysis on the effectiveness of the McKenzie MMDT for adult patients with neck pain.