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Objective: To compare the outcome and comparative efficacy of spinal manipulation and Mulligan sustained natural apophyseal glides in patients with mechanical upper back pain. Study Design: Quasi-experimental study. Place and Duration of Study: Riphah International University, Lahore Pakistan, from June to Dec 2020. Methodology: A sample of 26 patients with upper back pain was included. Subjects were distributed in two Groups: Group-A got spinal manipulation along with central sustained natural apophyseal glides treatment, and Group-B was treated with Mulligan-based central sustained natural apophyseal glides treatment. Faces pain scale, MODI questionnaire, and goniometer were used as data collecting tools. Pre-treatment and post-treatment values after 12 treatment sessions measured. Results: Pain decreased to a greater extent in the treatment of the Spinal Manipulation-Group with a mean value 1.85±1.28 as compared to 5.08±1.04 to Group-B (The p-value was <0.001). Oswestry disability index score decreased to a greater extent in post-treatment of Spinal Manipulation Group with a mean value of 16.85±3.16 as compared to Group-B, with a mean difference of 39.62±8.63 (The p-value was <0.001). Conclusion: The study results were statistically significant. Both spinal manipulation and central Mulligan central sustained natural apophyseal glides are well-accepted methods of treatment for subjects with upper back pain.