Background: The Makkah region is the most populated region in Saudi Arabia. Studying medication adherence levels may help to improve general health outcomes and decrease overall health care expenditures. Methods: We used the ARMS scale to assess medication adherence. Bivariable analysis of medication non-adherence was performed. Simple and multiple logistic regression models were built to identify factors associated with medication non-adherence. Results: Participants from the Makkah region were more than two times more likely to be non-adherent to their medications compared to other regions (adjusted OR = 2.58, 95% CI: 1.49–4.46). Patients who dispensed their prescriptions at their own expense were two times more likely to be non-adherents (adjusted OR = 2.36, 95% CI: 1.11–4.98). Patients who had a monthly income ≤6000 SR were almost two times more likely to be non-adherents (unadjusted OR = 1.73, 95% CI: 1.05–2.84). Conclusion: Medication adherence is one of the most important factors to help managing the disease. We found that Makkah chronic patients are more likely to be non-adherent with their medications compared to other regions’ patients. Moreover, we found that lower monthly incomes and paying for medications out-of-pocket were significant predictors of medication non-adherence.