Background: This research was designed to understand factors influencing Motor Vehicle Crashes (MVCs) on or near the Hualapai Tribe’s reservation in northwestern Arizona. The goal is to enable the Tribe to develop and implement a locally relevant MVC intervention program. The specific aims were to: i) compile and analyze 2010-2016 MVC data from Hualapai and federal sources to assess distributions of frequency, rates, high risk-locales, causes, days, times, age and sex of the drivers, in addition to assessing related conditions; ii) document local perceptions of environmental, social, and behavioral barriers to safe driving practices, and knowledge of MVC risk factors and existing tribal laws; and iii) provide evidence-based recommendations using the results from quantitative and qualitative data analyses. Approach/Methods: The research process applied a Community-Based Participatory Research approach and mixed methods using: a) secondary data analyses of records from six tribal programs and Indian Health Service (IHS), and b) qualitative analyses of data from two focus groups and field documents. Sensitivity analyses were conducted of IHS and Tribal Driving Under the Influence (DUI) data, using the 2010 U.S. Census as the denominator after adjusting for an undercount of up to 25%. Descriptive statistics, Fisher’s Exact Test, and linear and logistic regressions were used to examine significance. MVCs per 10 miles per year were estimated for State Route 66 and Diamond Bar Road/Grand Canyon West on or near the reservation due to higher numbers of crashes. Statistical process control charts, especially g-charts monitoring time between events, were plotted to examine the stability in the number of MVCs over time for each road. NVivo11Pro© was used to code and analyze the focus group data, guided by both inductive and deductive theories. Results: Driver’s seatbelt use in the Hualapai community increased from 2010 to 2012 (p < .0005), and reported DUIs decreased from 2010 to 2016 (p = .027). Similarly, car/booster seat use improved from 2014 to 2015 (p < .0005). Two hundred and fifty (N = 250) MVC-related injuries were registered at IHS facilities for Hualapai community members between 2006 and 2015. The highest rate, 22.4%, was observed in 15- to 24-year-olds, followed by 21.6% in 55- to 64-year-olds. For several combinations of numerators and denominators, sensitivity analysis of the IHS data shows a clear disparity between the Tribe’s MVC rate compared to the 2008 U.S. rate of 771.4 nonfatal injuries per 100,000 persons and the national goal for Healthy People 2020 (694.3 nonfatal injuries/100,000 persons). The major themes emerged from qualitative analyses of the focus groups were: i) unsafe traffic infrastructures, ii) DUI, iii) repeated DUI offenders driving on the reservation, and iv) a perception of lenient tribal traffic laws and enforcement on the reservation. Using study results, five Public Service Announcements were co-developed to inspire community-members to continue the trends noted from 2010-2016 and be aware of continued risks. Conclusions: MVCs are a multidimensional issue needing communitywide awareness of the range of risk factors. An intervention that addresses human and structural risks requires an alliance of tribal programs and external partners (e.g., IHS, university, federal, and state). Recommendations: Local recommendations include providing school- and institution-based education about alcohol/alcoholism and DUI consequences, and ongoing culturally and locally relevant communitywide education through the local newsletter and radio station.