Migraine is a common neurological disorder that substantially impacts individuals’ health and quality of life. This study aimed to estimate the prevalence of migraine and identify factors associated with it among patients attending primary healthcare centers (PHCs) in Saudi Arabia. We conducted a cross-sectional study from March to July 2023, involving 14,239 participants from 48 PHCs within Health Cluster 2 in the Riyadh region of Saudi Arabia. We collected data on participants’ sociodemographic characteristics, behavioral risk factors, and existing comorbidities using a validated questionnaire. Migraine status was determined based on participants’ self-reported prior physician diagnosis of migraine. To identify factors independently associated with migraine, we used multivariable logistic regression analysis. The adjusted odds ratios (AORs) and their 95% confidence intervals (CIs) were calculated to show the strength of these predictors. The prevalence of migraine was 5.9%. In the multivariable analysis, males had significantly lower odds of migraine compared to females (AOR = 0.69, 95% CI [0.59, 0.80], P < .001). Individuals with insurance coverage had higher odds of migraine (AOR = 2.44, 95% CI [2.11, 2.82], P < .001). Smoking (AOR = 2.44, 95% CI [2.05, 2.92], P < .001), and exercise (AOR = 1.46, 95% CI [1.18, 1.82], P < .001) were associated with higher odds of migraine. Several comorbidities were also significantly associated with migraine: obesity (AOR = 6.08, 95% CI [4.95, 7.47], P < .001), hypercholesterolemia (AOR = 2.59, 95% CI [2.07, 3.25], P < .001), hypertension (AOR = 1.47, 95% CI [1.15, 1.86], P = .002), and heart disease (AOR = 3.25, 95% CI [2.55, 4.15], P < .001). In this Saudi Arabian population, female sex, insurance coverage, smoking, obesity, hypercholesterolemia, hypertension, and heart disease were identified as significant predictors of migraine. These findings highlight the need for targeted preventive strategies and integrated care approaches addressing modifiable risk factors and comorbidities to reduce the burden of migraine.