Erenumab is a monoclonal antibody that mediates calcitonin-gene-related peptide (CGRP), a pro-inflammatory polypeptide implicated in migraine pathology, by targeting its receptor. To date, no clinical trial has evaluated combination therapy with both erenumab and onabotulinumtoxinA therapy for the treatment of chronic migraine. We conducted a retrospective chart review of 78 patients to investigate if the addition of erenumab to patients with chronic migraines receiving onabotulinumtoxinA had a decrease in their total monthly headache days (MHDs) and monthly migraine days (MMD). At baseline, while on onabotulinumtoxinA, mean MHDs were 22.5 ± 8.7 and mean MMDs were 15.8 ± 8.3, and 65 patients (83.3%) failed at least three preventative therapies. Our results demonstrated a significant reduction in MHDs and MMDs at 30- (-6.8 MHDs; p < 0.001, -7.0 MMDs; p < 0.001), 60- (-7.2 MHDs; p < 0.001, -6.7 MMDs; p < 0.001), and 90 days (-8.1 MHDs; p < 0.001, -7.4 MMDs; p < 0.001). Thus, the results of this study suggest favorable outcomes with the addition of erenumab to patients who were still suffering while receiving onabotulinumtoxinA therapy. Additional investigation is needed to determine if erenumab in combination with onabotulinumtoxinA has an enhanced effect on the modulation of CGRP release from peripheral unmyelinated C fibers while also blocking CGRP receptors in the myelinated A-delta fibers.