This research investigated the extents, trends/patterns, characteristics and associated causative factors of road traffic crashes in Amhara Regional State for the last ten years, 2009/10-2018/19. It also provided regional maps showing spatial patterns of road traffic crashes and assess the regional road safety institutional capacity, interventions, and their effectiveness. The essential data necessary for the study was collected from the yearly road traffic crash records of the police and formal and informal interviews, observations, and review of secondary data. A descriptive and statistical analysis is used for describing the trends, characteristics, and causes of road traffic crashes and for correlation and modeling of crashes accordingly. ArcGIS software is used to visualize spatial patterns. The World Bank guidelines are used to assess the effectiveness and efficiency of road safety institutional management. There has been a clear increasing trend in the number of road traffic crashes in Ethiopia and in Amhara region from 2009/10 to 2018/19. Although the crash severity indicates a decreasing trend at the national level, deaths, and non-fatal injuries per 1,000 rates in Amhara region are rising considerably. In Amhara region, during the last ten years, the number of fatal crashes increased by average rate of 2.89%, and fatalities by 7.6%. Road and population density, paved road length, and urbanization rate at each Woredas of the region were significantly associated with total and fatal crashes. Of 6,492 fatal road crashes reported in ten years period, 73.31%, 3.9%, 3.10% and 0.46% were caused due to drivers’ error, vehicle defects, pedestrian error, and road condition/environment, respectively. Among the various reasons, as reported by police, causing numerous fatal road traffic crashes in the region, failure to give way for pedestrians (27.14%) and over speeding (23.60%) contributed much to the misery of road crashes. Minibuses, trucks, and buses involved in 54.92% of fatal crashes. The majority fatal road crashes are occurring on principal arterial roads (52.71%). The share of rural village areas, agricultural areas, and residential areas in total fatal crashes is 75.11%. The economically active age group is the most vulnerable population group. Among all road user groups, the number of pedestrians killed by road traffic crashes is higher (53.12%). A large percentage of pedestrians who are victims of RTCs are farmers (41.36%). The spatial distribution of road traffic crashes in 129 Woredas and 45 towns mapped using Arc GIS software revealed that the highest number of road traffic crashes are registered in areas traversed by major highways. The research also pointed out the areas with high road network length are crash-prone areas. Furthermore, the study results indicate that there is a poor road safety culture and attitudes in the region. This is largely due to weak leadership and coordination for road safety, lessening priority for allocating resources, and diminishing capacity for road safety interventions, mainly driven by consistently low commitment to road safety works, reduced interest and participation of road safety stakeholders, private sector, and civil societies to mitigate the challenges. Urgent road traffic crash preventive measures and prompt treatment of the victims are warranted to reduce the burden of a road traffic crash. Strengthening safety regulations and enforcement of safety rules will help in reducing the occurrence of road traffic crashes. Awareness creation, educations, increased investments for transport facilities, use of modern technologies, traffic control measures, the motivation of traffic police officers and strong leadership and coordination for road safety are vital to reduce road traffic crashes and its outcome.