Background: OnabotulinumtoxinA (OnabotA) is considered effective in in patients with chronic migraine (CM) who failed on traditional therapies. This study was designed to evaluate the effect of OnabotA injection series on migraine outcome, negative emotional states and sleep quality in patients with CM. Methods: A total of 190 patients with CM (mean (SD) age: 39.3 (10.2) years; 87.9% were female) were included. Data on Pittsburgh sleep quality index (PSQI), headache frequency and severity, number of analgesics used, Migraine Disability Assessment Scale. (MIDAS) scores and Depression, Anxiety and Stress Scale (DASS-21) were evaluated at baseline (visit 1) and 4 consecutive follow up visits, each conducted after OnabotA injection series; at week 12 (visit 2), week 24 (visit 3), week 36 (visit 4) and week 48 (visit 5) to evaluate change from baseline to follow up. Results: From baseline to visit 5, significant decrease was noted in least square (LS) mean headache frequency (from 19.5 to 8.4, rho = 0.002), headache severity (from 8.1 to 6.1, rho = 0.017), number of analgesics (from 26.9 to 10.4, rho = 0.023) and MIDAS scores (from 67.3 to 18.5, rho < 0.001). No significant change from baseline was noted in global PSOI and DASS-21 scores throughout the study. Conclusions: Our findings revealed that OnabotA therapy was associated with significant improvement in migraine outcome leading to decrease in headache frequency and severity, number of analgesics used and MIDAS scores. While no significant change was noted in overall sleep quality and prevalence of negative emotional states, patients without negative emotional states at baseline showed improved sleep quality throughout the study.