Openness to diversity and challenge (ODC) has been identified as an important educational aim in higher education research, educational philosophy, and popular discourse. Yet, the relationship between college students’ activism orientation, their unique social positions, and their development of ODC in contexts of political polarization remains underexplored. This study explores these relationships using a mixed method (quantitatively driven + qual) approach guided by an ecological framework. Analyzing survey data collected between 2017 and 2019, we found that students’ activism orientation scores are significantly positively associated with their ODC. Our qualitative analysis revealed several factors that students perceive as supporting their development of perspective taking—(a) campus diversity, including political diversity; (b) academic course environments; (c) student organizations and campus events; and (d) informal interactions with peers—as well as several barriers to perspective taking—(a) political climate on campus; (b) politicized racism, anti-immigrant, antitrans, and other forms of unjust bias; and (c) resistance to politically conservative viewpoints. Overall, our study suggests several factors may support college students’ development of ODC, including microsystem-level exposure to diverse campus environments and informal interactions with peers within those environments, notably engagement in activism and exposure to other students’ activism. When encouraging educational aims like ODC, college and university personnel designing microsystem-level interventions should be aware of and responsive to the unique ways that students may experience these efforts depending on their social positions—and in particular their experiences of marginalization—within and beyond the campus environment.