The Global burden of disease study ranked migraine as the sixth most common disorder worldwide in 2016, with significant social and economic sequelae. In this study, we assessed the efficacy of different Calcitonin gene-related peptide (CGRP) receptor blockers as potential pharmacological approaches and compare them to placebo using the systematic review (SR) and network meta-analysis (NMA) approach. We performed a computerized search of SCOPUS, PubMed, Cochrane central, and Embase databases through January 2019 and included randomized controlled trials (RCTs), which were performed on episodic and chronic migraine patients who used Erenumab, Eptinezumab, Fremanezumab, or Galcanezumab. The combined analysis revealed that after six, eight, and twelve weeks of intervention, the medications with the most potent effects in comparison to placebo were Fremanezumab 900 mg, (SMD = -0.55, 95% CI [-0.97, -0.12]); Erenumab 140 mg, (SMD = -0.51, 95% CI [-0.61, 0.41]); and Erenumab 140 mg, (SMD = -0.48, 95% CI [-0.571, 0.39]), respectively. For chronic migraine patients, Fremanezumab 900 mg, Erenumab 140 mg, in addition to Erenumab 70 mg, were associated with the highest efficacy after 6, 8, and 12 weeks, correspondingly. The analysis of combined groups data (Chronic and Episodic) showed that Fremanezumab was the most effective drug after six weeks, where Erenumab was the most effective after 8 and 12 weeks. The current evidence retrieved from this NMA suggests that Fremanezumab was the most effective anti-migraine medication in decreasing MHDs per month after six weeks in both chronic and episodic patients.