Despite clear financial and societal benefits of pursuing degrees in science, technology, engineering, and mathematics (STEM), Indigenous students are underrepresented in undergraduate STEM degree programs and STEM industries. While existing literature uses qualitative methods to understand the experiences of Indigenous STEM students, there is a scarcity of quantitative work focusing on the college pathways of Indigenous students. This study uses logistic regression to examine the STEM pathways of Indigenous students who attended high school in Nebraska. Prior research demonstrates that taking STEM courses, including Algebra 2, biology, chemistry, and physics, relates to college enrollment. In particular, this article considers if there is a relationship between taking advanced math and science classes in high school and postsecondary enrollment. Findings indicate that taking Algebra 2 in high school is significantly related to enrolling in college. Similarly, taking Algebra 2 or two advanced lab science courses (biology, chemistry, and/or physics) is related to planning to major in a STEM field. However, only about 42% of Indigenous students were enrolled in Algebra 2, compared to about 74% of White students in the same cohort. Given these findings, high school districts and state policymakers need to consider how unequal opportunities to learn math and science could be inhibiting postsecondary outcomes of Indigenous students. Additionally, postsecondary administrators should acknowledge the barriers that Indigenous students face in secondary STEM education and consider revising admissions standards and support services to attend to the needs of this student population.