Introduction: The management of chronic illnesses commonly includes a long-term pharmacological approach. Although these medications effectively control disease, their full benefits are often not realized because approximately 50% of patients do not take their medications as prescribed. Medication adherence has become a big concern to clinicians and healthcare systems in Saudi Arabia and worldwide because of growing evidence associating nonadherence with adverse outcomes and higher costs of care. Despite it being a well-recognized problem, few studies have investigated medication adherence in Saudi Arabia. Therefore, this study aims to gain a better perspective on medication adherence among patients with chronic diseases in Saudi Arabia. Method: A questionnaire-based cross-sectional study was conducted among patients with chronic diseases in the Makkah region, Saudi Arabia, from 1 May to 31 July 2021. Patients aged 18 years and above who were taking prescribed or over-the-counter medications were included. Descriptive statistics were used to describe the participants’ characteristics, and categorical variables were reported as frequencies and percentages. A Chi-square test was used to test the relations between variables. Results: In total, 239 participants were included in the study. Females represented 62% of the participants. In terms of the history of chronic diseases, 44% had hypertension, 40% had diabetes mellitus, 21% had heart diseases and 9% had asthma. Nearly half (49%) of participants did not follow up regularly with a primary healthcare center and 42% said that they had forgotten to take their medications in the past. However, most of the participants (78%) stated that they took their medicine as instructed by their doctor or pharmacist, and 61% took their medications on time. The majority of participants (85%) said that the pharmacist explained the method of using the medications and the instructions for use, while 30% thought that the medications they took were too much. In regard to the reasons for medication nonadherence, having no specific reasons for medication nonadherence was the most common cause for nonadherence in our study. The relationship between patients taking medications as instructed by a healthcare provider (the doctor or pharmacist) and the healthcare provider giving clear instructions to patients about medication use was significant (p < 0.001). Conclusions: Failure to adhere is a significant problem that not only affects the patient but also the healthcare system. Additional research is needed to monitor medication adherence and identify factors contributing to this problem to provide successful strategies to improve medication adherence in Saudi Arabia.