Both calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and OnabotulinumtoxinA (botox) are used in the prevention of chronic migraines. However, it is not clear which is more effective overall. This review will compare the efficacy, side effects, cost-effectiveness, and other factors between CGRP mAbs and botox. We searched Pubmed and Google Scholar using the keywords migraines, CGRP mAbs, botox, efficacy, side effects, aura. All articles, including case-control/cohort studies, case series, case reports, randomized control trials, traditional/systematic reviews, were analyzed. CGRP mAbs and botox both reduce the frequency of migraines in patients. Patients have reported they decreased migraines' frequency and intensity in several studies after being given each medication. While CGRP mAbs are more recent medications, botox has been studied for more than a decade as a migraine preventative. Both drugs have minor short-term side effects, but some CGRP mAbs may cause persistent constipation too. CGRP mAbs are self-injected every month, and botox is physician-injected every three months, making it easier to stay compliant. While both medications are expensive, botox has a lower cost over time. Botox is more effective prophylaxis of migraines based on the articles that were reviewed. While both CGRP mAbs and botox are efficacious and tolerable, botox has been studied longer, has fewer side effects, is more cost-effective, and is easier to comply with.