Background: Road traffic injuries (RTIs) and deaths constitute a serious preventable global public health problem. Aims: To analyse time trends of age-standardized mortality rates and disability-adjusted life years (DALYs) caused by RTIs in 23 Middle East and North Africa (MENA) countries; and to assess the correlation between national implementation of best practice for road safety recommended by the World Health Organization, national income level, and RTI burden. Methods: Time trend analysis over 17 years (2000–2016) was conducted using Joinpoint regression. An overall score was calculated for each country to assess implementation of best practice for road safety. Results:Mortality decreased significantly (P < 0.05) in Islamic Republic of Iran, Jordan, Kuwait, Lebanon, Morocco, Oman, Qatar, and Tunisia. In most MENA countries, DALYs increased but they significantly decreased in the Islamic Republic of Iran. The score calculated varied widely among the MENA countries. In 2016, no correlation was identified between the overall score and mortality and DALYs. National income was not associated with RTI mortality or the calculated overall score. Conclusion: Countries in the MENA region had varying levels of success in reducing the burden from RTIs. During the Decade of Action for Road Safety 2021–2030, MENA countries can achieve optimal road safety by implementing measures that are customized for the local context, such as law enforcement and public education. Other focus areas for improving road safety are building capacity in sustainable safety management and leadership, improving vehicle standards, and addressing gaps in areas such as use of child restraint