From 2009 to 2018, overall suicide rates in the United States increased by 20.3% and increased by 43.5% among non-Hispanic American Indian and Alaska Native (AI/AN) communities. Combining years 2009 through 2018, suicide rates per 100 000 population among non-Hispanic AI/AN adolescents and young adults aged 15 to 34 years were 2 to 4 times higher than those of adolescents and young adults of other races and ethnicities. An estimated 14% to 27% of non-Hispanic AI/AN adolescents attempted suicide during that time. The elevated rates of suicidal behavior among non-Hispanic AI/AN adolescents and young adults reflect inequities in the conditions that create health. In this topical review, we describe school-based educational efforts that are driven by local AI/AN communities, such as the American Indian Life Skills curriculum, that teach stress and coping skills and show promise in reducing suicidal ideation attempts and fatalities among AI/AN adolescents. Using a social-determinants-of-health lens, we review the availability and quality of employment as an important influencer of suicidal behavior, as well as the role of the workplace as an environment for suicide prevention in AI/AN communities. Working with tribal, state, local, and federal colleagues, the public health community can implement programs known to be effective and create additional comprehensive strategies to reduce inequities and ultimately reduce suicide rates.