© 2018 John Wiley & Sons, Ltd. Background and Purpose: Neck pain is the fourth leading cause of disability in the United States and exerts an important socio-economic burden around the world. The aims of this study were to determine the effectiveness of deep and superficial flexor muscle training in addition to home-based exercises in reducing chronic neck pain and anxiety/depression levels. Methods: This was a prospective cohort study. Patients between 18 and 65 years old with chronic neck pain were eligible to participate if they had disability levels at least 5 out of 50 on the Neck Disability Index. Patients were divided into three groups: Group A received deep neck flexor and home-based exercises; Group B received superficial muscle and home-based exercises; and Group C received home-based exercises only. The Numeric Pain Rating Scale (NPRS), Neck Disability Index, and Hospital Anxiety and Depression Scale were administered at baseline and 7 weeks later. Results: The highest improvements in pain intensity levels were observed in Group A with 4.75 (1.74) NPRS points, and the lowest were in Group C with 1.00 (1.10). The highest reductions in anxiety and depression levels were noted in Group A (2.80) and Group B (1.65), respectively. The highest improvements in pain intensity levels were observed among Groups A versus C with 2.80 (0.52) NPRS. The highest reductions in anxiety and depression levels were noted among Groups A versus C with 1.75 (1.10) points and Groups B versus C with 1.60 (0.90) points, respectively. Conclusions: Deep and superficial flexor muscle training along with home-based exercises is likely to reduce chronic neck pain and anxiety/depression levels by a clinically relevant amount. Future larger scaled randomized controlled trials are warranted to further support these findings.