Background Migraine is a major public health issue that leads to frequent visits to medical care. It is generally considered a disabling disease among individuals below the age of 50 years old predominantly seen in females. Migraine headache has a strong influence on disability, functional impairments, and psychological effects. The majority of the physicians fail to address the degree and extent of impediment caused by a migraine, which contributes to low quality of life and disability. Thus, this study aims to assess the health-related quality of life (QOL) and disability among migraine sufferers in AlAhsa, Saudi Arabia. Material and methods This descriptive cross-sectional study was carried out in the neurology clinics at King Fahad Hospital-Hofuf, AlAhsa, Saudi Arabia, from May to August 2021. The data were collected through a self-administered questionnaire. The migraine-specific quality of life questionnaire (MSQ), version 2.1, was used. MSQ is measured in three domains, including role function restrictive (RR), preventive (RP), and emotional function (EF). Disability related to migraine was assessed by the Migraine Disability Assessment Test (MIDAS). MIDAS classifies disability from no disability to severe disability. Two-tailed with an alpha level of 0.05 considering the significance of a p-value less than or equal to 0.05. The mean scores of QOL domains were compared by one-way analysis of variance (ANOVA) and independent t-tests. Results A total of 101 out of 359 participants were identified to have a migraine. Eighty-two participants met the inclusion criteria, 75.6% were females. The age of the participants ranged from 18 to more than 45 years with a mean age of 36.4 ± 11.9 years old. The mean score of QOL in the restrictive, preventive, and emotional domains were 46.3% ± 21.5%, 52.1% ± 24.3%, and 61.5% ± 30.8%, respectively. More than half of the participants (57.3%) suffered from a severe disability caused by migraines as compared to 20.7% with a moderate disability. Low QOL scores were associated with females and a significant relationship was found between migraine-associated disability and patients’ emotional function in QOL. Conclusion Clinicians should routinely evaluate disability related to migraine and QOL as a complementary approach to migraine patients to ensure that patients are receiving proper treatment and whether additional strategies are needed or not.