BACKGROUND: Knee is the most affected joint in osteoarthritis (OA) and accounts for almost four-fifths of the burden of OA globally. We aimed to explore the prevalence, incidence, trends, and burden of knee OA during 1990-2019 in the Middle East and North Africa (MENA) region, using the Global Burden of Disease (GBD) study data. METHODS: This is an epidemiological study based on the GBD data from 1990 to 2019 on knee OA in MENA countries. The prevalence, incidence, and years lived with disability (YLD) numbers of knee OA were obtained for both genders. Similarly, age-standardized rates of these indexes per 100,000 people and the proportion of total YLD caused by knee OA in each country and for the MENA region were evaluated. RESULTS: The prevalence of knee osteoarthritis in the MENA region increased 2.88-fold, from 6.16 million cases to 17.75 million, between 1990 and 2019. Furthermore, in 2019, knee osteoarthritis accounted for approximately 1.69 million (95% UI 1.46-1.95) incident cases in MENA. The age-standardized prevalence was higher in women between 1990 (3.94% [95% UI 3.39-4.55] in women and 3.24% [95% UI 2.79-3.72] in men) and 2019 (4.44% [95% UI 3.83-5.10] in women and 3.66% [3.14-4.21] in men). Total YLDs due to knee osteoarthritis increased by more than 2.88-fold, rising from 196.29 thousand [95% UI 97.17-399.29] in 1990 to 564.66 thousand [95% UI 275.06-1,150.68] in 2019. In the year 2019, Kuwait, Turkey, and Oman had the highest age-standardized prevalence (4.42% [95% UI 3.79-5.08]), YLD (132.41 [95% UI 65.79-267.56] per 100 000), and increase (21.17%) in YLD compared with 1990 in MENA region, respectively. CONCLUSION: The prevalence of and YLDs due to knee OA in MENA has escalated over the last three decades. Considering the expanding burden of knee OA in MENA, policymakers should be more concerned to implement preventive strategies.