This study aims to identify potential injury-related mortality disparities for American Indians/Alaskan Natives (AI/ANs) within the rural counties of one US state, Wisconsin. The Wisconsin Interactive Statistics on Health database was used to compare injury-related mortality for AI/ANs and whites in rural counties from 2016 to 2020. Both unintentional and intentional injuries were examined. This study found that AI/ANs were 62% more likely to die of an injury compared with whites in rural counties (relative risk (RR): 1.62; 95% CI: 1.41 to 1.86). When looking at injury-related mortality across various age groups, the 18–44-year-old age group had the largest injury-related mortality gap for AI/ANs compared with whites (RR: 2.85; 95% CI: 2.36 to 3.44). This study presents evidence that AI/ANs face significant injury-related mortality disparities compared with whites in rural counties.