As student bodies in higher education become more diverse, efforts to address diversity, equity, and inclusion (DEI) have also increased. Sexual and racial minoritized students are often systematically pushed out of higher education and currently report concerning dropout rates. Thus, research using an intersectional lens on oppressive experiences linked to academic outcomes is needed. This study aimed to unpack different types and levels of impact from intersectional microaggressions (racism and heterosexism) among lesbian, gay, bisexual, transgender, queer (LGBTQ) Black, Indigenous, and people of color (BIPoC) college students using an intersectional approach. Specifically, we assessed if the psychological distress associated with intersectional microaggressions mediated its relationship with school persistence. Additionally, we tested factors such as cisgender privilege, internalized racism, or internalized heterosexism as moderators for this model. Using a moderated mediation analysis (Model 13; Hayes, 2012), results supported our hypothesis that psychological distress helps explain (mediator) the link between intersectional microaggressions and school persistence. Furthermore, results for the first moderator—cisgender privilege showed this serving as a protective factor for cisgender people when experiencing these intersectional microaggressions. Results for internalized racism as a second moderator interacting with intersectional microaggression and cisgender privilege showed significant effects at all levels for gender-expansive participants, but not for cisgender participants. Finally, internalized heterosexism was a significant moderator for gender-expansive participants when experiencing intersectional microaggression in relation to psychological distress and school persistence. Our findings highlight immediate implications around education and well-being for LGBTQ+ BIPoC college students. We discuss limitations and implications that can better guide DEI efforts to serve these minoritized groups.